Oncology Probes

KREATECH DiagnosticsProduct Guide

IntroductionDear valued customerWelcome to our new Product Guide 2010 ! This catalog includes a lot of new productswhich we have added into our portfolio throughout last year and we would like tospecifically highlight the following sections:• Our new line of CISH products (page 92)• New multicolor probe panels for preimplantation genetic screening (page 66)• Our unique target labeling products based on ULS• And many new FISH probes, e.g. for prostate cancer (TMPRSS2-ERG), glioma andsarcoma (CDK-4), our solid tumor probes MDM4, FGFR1, and our new MYC breakapartprobe for lymphomaWe hope that you will find a lot of products in this catalog suitable for your dailyresearch. If you have any additional questions do not hesitate to contact us or visitwww.kreatech.com to find the most up-to-date information about our products.Kreatech DiagnosticsIntroduction3

Product Selection GuideI want to use a brightfield microscopeAPPLICATIONPathologyUniStarTwinStar9292Hematology Probes10OncologyKREAvital vital Lymphocyte Medium94Solid Tumor Probes46MultiStar 24 FISH66Preimplantation Genetic ScreeningPreimpScreen67CISHPrenatal Probes68IN SITUHYBRIDIZATIONPrenatal DiagnosticsKREAvital Prenatal MediumMicrodeletion Probes9470Postnatal ScreeningFISHSub-Telomere Probes82Satellite Enumeration Probes84Chromosome IdentificationWhole Chromosome Probes86Arm Specific Probes88Product Selection GuideI want to use aPOSEIDON probeI want an individualDNA probe for FISHI want to label myown DNA for FISHBand Specific ProbesMouse FISH ProbesCustomized DNA ProbesFISHBright labeling Kits8890911004

Table of ContentsIntroduction 3Table of Contents 5Chromosome Index 6HUGO Gene Symbols 8Molecular cytogeneticsPOSEIDON FISH Probes 10Oncology Probes 10Hematology 10Solid Tumors 46Preimplantation Genetic Screening 66Prenatal Probes 68Microdeletion Probes 70Sub-Telomere Probes 82Satellite Enumeration Probes 84Whole Chromosome Probes 86Arm Specific Probes 88Mouse FISH Probes 90Customized DNA Probes 91CISH 92Unistar 92Twinstar 92Cell Culture Media 94Equipment 97Kits and Reagents 98FISHBright Labeling Kits 100Microarray labelingThe ULS Labeling Technology 103DNA Labeling 104RNA Labeling 106Protein Labeling 108General Nucleic Acid Labeling 109Antibody Labeling 110KREApure 111Technical Appendix 112Terms and Conditions 114CE marking & ISO certificates 115Product Index 116How to order 126International Distributors 127Table of Contents5

HUGO Gene SymbolsThe table below gives the approved HUGO Gene Symbol and aliases used for every gene in our Poseidon FISHDNA probes according to the HUGO Gene Nomenclature Committee (HGNC).ChromosomepositionGenes involvedHUGO GeneSymbolsAliases Cat.# PageHUGO Gene Symbols81p36 CHD5 CHD5 KBI-1050739KBI-10712531q32 MDM4 MDM4 MDMX KBI-10736 541q21 S100A10 S100A10 P11, 42C, CLP11KBI-1050337KBI-10507392p24 MYCN MYCN bHLHe37, N-myc KBI-10706 522q11 LAF AFF3 MLLT2-like, LAF4 KBI-10706 523p25 PPARy PPARG PPARG1, PPARG2, NR1C3, PPARgamma KBI-10707 513q26 EVI MECOM MDS1-EVI1, PRDM3KBI-1020428KBI-1020528KBI-10110213q26 hTERC TERC TR, hTR, TRC3, SCARNA19KBI-1020428KBI-1020528KBI-10704503q27 BCL6 BCL6 ZBTB27, LAZ3, BCL5, BCL6AKBI-1060744KBI-10730644p16 FGFR3 FGFR3 CEK2, JTK4, CD333 KBI-10602 364p16 WHSC1 WHSC1 MMSET, NSD2 KBI-40107 784q12 CHIC2 CHIC2 BTLKBI-1000316KBI-10007164q12 FIP1L1 FIP1L1 DKFZp586K0717KBI-1000316KBI-10007164q12 PDGFRA PDGFRA CD140a, PDGFR2KBI-1000316KBI-10007165p15 CTNND CTNND2 NPRAP, GT24 KBI-40106 78KBI-10208255p15 hTERT TERT TRT, TP2, TCS1, hEST2, EST2KBI-1021026KBI-1070959KBI-40113745q31 CDC25C CDC25C5q31 EGR1 TIS8, G0S30, NGFI-A, KROX-24, ZIF-268, AT225, ZNF225KBI-10209KBI-10210KBI-10709KBI-10208KBI-10209KBI-10210KBI-107095q33 CSF1R CSF1R C-FMS, CSFR, CD115KBI-1020925KBI-10210265q33 PDGFRB PDGFRB JTK12, CD140b, PDGFR1KBI-1000417KBI-40064665q33 RPS14 RPS14 EMTBKBI-1020925KBI-10210265q35 NSD1 NSD1 ARA267, FLJ22263, KMT3B KBI-40113 746q21 SEC63 SEC63 SEC63L, PRO2507, ERdj2KBI-10105KBI-10109KBI-105042023387p11 EGFR, Her1 EGFR ERBB1 KBI-10702 597q11 ELN ELN WBS, WS, SVAS KBI-40111 767q11 LIMK1 LIMK1 LIMK KBI-40111 767q22 CUTL1 CUX1 CDP, CDP1, CUX, CUT, Clox, CDP/Cut, CDP/Cux, Cux/CDP, CASP, GOLIM6KBI-1020226KBI-10207277q31 C-MET MET HGFR, RCCP2 KBI-10719 608p21 PNOC PNOC PPNOC KBI-10503 378p12 FGFR1 FGFR1 H2, H3, H4, H5, CEK, FLG, BFGFR, N-SAM, CD331 KBI-10737 498q21 ETO RUNX1T CDR, ETO, MTG8, ZMYND2 KBI-10301 298q24 C-MYC MYC c-Myc, bHLHe399p21 p16 CDKN2A CDK4I, p16, INK4a, MTS1, CMM2, ARF, p19, p14, INK4, p16INK4a, p19Arf9q34 ABL ABL1 JTK7, c-ABL, p150KBI-10106KBI-10109KBI-10603KBI-10611KBI-10704KBI-10402KBI-10710KBI-10005KBI-10006KBI-10008KBI-10009KBI-10508KBI-10508389q34 ASS ASS1 CTLN1KBI-1000613KBI-1000814KBI-100091410q23 PTEN PTEN MMAC1, TEP1, PTEN1 KBI-10718 6011q13 BCL1 CCND1 U21B31 KBI-10604 41KBI-106044111q13 CCND1 CCND1 U21B31KBI-1060535KBI-1060943KBI-107346211q13 MYEOV MYEOV OCIM KBI-10605 3511q22 ATM ATM TEL1, TELO1KBI-10103KBI-10108KBI-1011419222311q23 MLL MLL TRX1, HRX, ALL-1, HTRX1, CXXC7, MLL1A, KMT2AKBI-10303KBI-10711252659252526592023404450335013131414383053

ChromosomepositionGenes involvedHUGO GeneSymbolsAliases Cat.# Page11q23 PLZF ZBTB16 PLZF KBI-10502 3612p13 TEL ETV6KBI-1040132KBI-104033312q13 CDK4 CDK4 PSK-J3 KBI-10725 5812q13 CHOP DDIT3 CHOP10, GADD153, CHOP KBI-10714 5612q13 GLI GLI1KBI-1010421KBI-101082212q15 MDM2 MDM2 HDM2, HDMX, MGC5370 KBI-10717 5813q14 DLEU DLEU1 LEU1, XTP6, NCRNA00021KBI-10102KBI-10113KBI-1050218223613q14 FKHR FOXO1 FKH1 KBI-10716 57KBI-10601KBI-10602KBI-1060314q32 IGH IGH@ IGHDY1, IGHKBI-10604KBI-10605KBI-10606KBI-10610KBI-1072915q11 SNRPN SNRPN SMN, SM-D, HCERN3, SNRNP-N, SNURF-SNRPN, RT-LI KBI-40109 7515q11 UBE3A UBE3A AS, ANCR, E6-AP, FLJ26981KBI-4011076KBI-401168115q22 SMAD6 SMAD6 HsT17432KBI-1050438KBI-105083815q24 PML PML MYL, TRIM19, RNF71KBI-10302KBI-40109KBI-4011030757615q26 IGF1R IGF1R JTK13, CD221, IGFIR, MGC18216, IGFR KBI-40116 8116p11 FUS FUS TLS, FUS1, hnRNP-P2 KBI-10715 5716q22 CBFB CBFB PEBP2B KBI-10304 3116q23 MAF MAF c-MAF KBI-10610 3517p13 AURKB AURKB Aik2, IPL1, AurB, AIM-1, ARK2, STK5 KBI-10722 6117p13 LIS PAFAH1B1 LIS1, PAFAH KBI-40101 77KBI-10011KBI-10112151917p13 p53 TP53 p53, LFS1KBI-1011322KBI-1011423KBI-10509KBI-10738376517p11 RAI1 RAI1 DKFZP434A139, SMCR, SMS, KIAA1820, MGC12824 KBI-40101 7717q11 NF1 NF1 KBI-40114 7417q12 ERBB2 ERBB2 NEU, HER-2, CD340, HER2KBI-1070147KBI-107354817q21 RARA RARA RAR, NR1B1KBI-1030230KBI-103053117q21 TOP2A TOP2AKBI-1072447KBI-107354817q22 MPO MPOKBI-1001115KBI-401147418q11 SYT SS18 SYT KBI-10713 5618q21 BCL2 BCL2 Bcl-2 KBI-10606 4118q21 MALT MALT1KBI-1060842KBI-107316419q13 CD37 CD37 TSPAN26KBI-1050937KBI-400646620q11 MAPRE1 MAPRE1 EB1KBI-10203KBI-10721KBI-1073327614820q12 PTPRT PTPRT RPTPrho, KIAA0283 KBI-10203 2720q13 AURKA AURKA BTAK, AurA, STK7, ARK1 KBI-10721 6120q13 ZNF217 ZNF217 ZABC1 KBI-10733 4821q22 AML RUNX1 PEBP2A2, AMLCR1 KBI-10301 2921q22 ERG ERG erg-3, p55 KBI-10726 6321q22 TMPRSS2 TMPRSS2 PRSS10 KBI-10726 63KBI-100051322q11 BCR BCR D22S662, CML, PHL, ALLKBI-1000613KBI-1000814KBI-100091422q11 CLH22 CLTCL1 CLTD, CLH22, CHC22 KBI-40102 71,7322q11 DGCR2 DGCR2 KIAA0163, LAN, IDD, DGS-C, SEZ-12KBI-40102KBI-4010322q12 EWS EWSR1 EWS KBI-10708 55KBI-4010222q13 SHANK3 SHANK3 SPANK-2, prosap2, KIAA1650, PSAP2KBI-40103KBI-40104Xp22 KAL KAL1 KALIG-1 KBI-40115 80Xp22 SHOX SHOX PHOG, GCFX, SS, SHOXY KBI-40112 79Xp22 STS STS ARCS KBI-40115 80Xp11 TFE3 TFE3 TFEA, bHLHe33KBI-1074165KBI-4005167Xq13 XIST XIST NCRNA00001, DXS1089, swd66 KBI-40108 7924,39,423640413541356371,7372,7371,7372,7372,73HUGO Gene Symbols9

Oncology probes - Hematology ProbesFrom the 25,000 genes in the human genome, approximately 350 genes have been causally linked to the developmentof cancer. Variant or aberrant function of these so-called cancer genes may result from changes in genome copy number(through amplification, deletion, chromosome loss, or duplication), changes in gene and chromosome structure (throughchromosomal translocation, inversion, or other rearrangements that lead to chimeric transcripts or deregulated geneexpression) and point mutations (including base substitutions, deletions, or insertions in coding regions and splicesites). The vast majority (90%) of cancer genes are mutated or altered through chromosomal aberrations in somatictissue, about 10% are altered in the germ line, thereby transmitting heritable cancer susceptibility through successivegenerations. In addition to high resolution chromosome banding and advanced chromosomal imaging technologies,chromosome aberrations in cancer cells can be analyzed with an increasing number of large-scale, comprehensivegenomic and molecular genetic technologies – including fluorescence in situ hybridization (FISH).Oncology Probes - Hematology ProbesChromosomal translocation (t) is the process by which a break in at least two different chromosomes occurs,with exchange of genetic material between the chromosomes.DescriptionPageChronic Myelogenous Leukemia (CML) 12Chronic Lymphocytic Leukemia (CLL) 18Myelodysplastic Syndrome (MDS) 24Acute Myeloid Leukemia (AML) 29Acute Lymphoblastic Leukemia (ALL) 32Multiple Myeloma (MM) 3410Lymphoma 40

Translocation, Dual-Fusion AssayDual-fusion, dual-color FISH assays for translocation utilizeslarge probes that span 2 breakpoints or flanking regionson the different chromosomes. Dual-fusion, dual-color FISHis optimal for detection of low levels of nuclei possessinga simple balanced translocation, as it greatly reduces thenumber of normal background nuclei with an abnormalsignal pattern.Translocation, Break-Apart or Split AssayFISH using dual-color, break-apart probes is very useful in theevaluation of genes known to have multiple translocationpartners; the differently colored probes hybridize to targetson opposite sides of the breakpoint of the affected gene.Translocation, Dual-Fusion AssayTranslocation, Break or Split AssayNormalChromosomesNormalInterphaseAberrantChromosomesAberrantInterphaseExpected signal pattern:In normal intact cells, two separate red and two separategreen individual signals will be visible, whereas a reciprocaltranslocation will generate two fused red/green signals(often appearing as single yellow signals), accompaniedby one red and one green signal (representing the normalchromosomes).NormalChromosomeNormalInterphaseAberrantChromosomesAberrantInterphaseExpected signal pattern:In normal cells two sets of red/green-fused signals(representing the two alleles) will be visible. In anabnormal diploid cell, in which one allele has been split bya translocation, a separated red and green signal will bevisible in addition to the normal fused signal.Oncology Probes - Hematology Probes11

Chronic Myeloproliferative Disorders (CMPD)Chromosomal translocations in chronic myeloproliferativediseases (CMPD) almost invariably result inexpression of constitutively activated fusion tyrosinekinases. The hallmark of these diseases is CML, wherethe BCR/ABL activated tyrosine kinase results fromthe balanced reciprocal Philadelphia chromosometranslocation t(9;22).Chronic Myelogenous Leukemia (CML) - BCR/ABL t(9;22)CML is a malignant chronic myeloproliferative disorder (MPD)of the hematopoietic stem cell. All CML have a t(9;22) causingfusion of the 3’ ABL region at 9q34 with the 5’ BCR region at22q11. This chimeric BCR/ABL gene encodes a constitutivelyactivated protein tyrosine kinase with profound effects on cellcycle, adhesion, and apoptosis. Understanding this process hasled to the development of the drug imatinib mesylate (Gleevec),the first in a new class of genetically targeted agents, this is amajor advance in cancer treatment. Several different approachesare used to analyze the BCR/ABL t(9;22)(q34;q11) by FISH eachproviding different details about this translocation.BCR/ABL Product FamilyThe Philadelphia chromosome is an abnormally shortchromosome 22 that is one of the two chromosomes involvedin a translocation with chromosome 9. This translocation t(9;22)(q34;q11) takes place in a single bone marrow cell and, throughthe process of clonal expansion, gives rise to the leukemia.ABL and BCR are normal genes on chromosomes 9 and 22,respectively. The ABL gene encodes a tyrosine kinase enzymewhose activity is tightly controlled. In the formation of thePh translocation, two fusion genes are generated: BCR-ABLon the Ph chromosome and ABL-BCR on the chromosome 9participating in the translocation. The BCR-ABL gene encodesa protein with deregulated tyrosine kinase activity.The presence of this protein in the CML cells is strongevidence of its pathogenetic role. The efficacy in CMLof a drug that inhibits the BCRABL tyrosine kinase hasprovided the final proof that the BCR-ABL oncoprotein isthe unique cause of CML. The Poseidon portfolio containsnow 4 different probes for BCR/ABL to suit all needs forthe detection of t(9;22) by FISH:BCR/ABL t(9;22) Dual-color, Dual-Fusion ProbeD22S940SHGC-147754ASS340 KBIGLC1340 KBABLBCRInterpretationguidelines forPoseidonBCR/ABL ProbesNormal Cell t(9;22) positive Cryptic insertion 9q34 to 22q11BCR/ABL t(9;22) Triple-color, Dual-Fusion Probe99q34NUP214D9S19911000 KB2222q11IGLL1SHGC-1074501000 KBOncology Probes - Hematology ProbesNormal Cellt(9;22) positiveWith del(22q11)Normal Cellt(9;22) positivet(9;22) positiveWith del(9q34)BCR/ABL t(9;22) Dual-color, Single-Fusion Extra Signal Probet(9;22) positiveBCR/ABL t(9;22) Dual-color, Single-Fusion Probe99SHGC-147754ASSABLNUP2149q34 D9S1991SHGC-147754ASSABLNUP2149q34 D9S1991SHGC-147754ASSABLNUP2149q34 D9S1991340 KB1000 KB340 KB1000 KB340 KB1000 KB2222D22S940IGLC1BCRIGLL122q11SHGC-107450D22S940IGLC1BCRIGLL122q11SHGC-107450D22S940IGLC1BCRIGLL122q11340 KB1000 KB340 KB340 KB92212Normal Cellt(9;22) positive

ON BCR/ABL t(9;22), FusionThe BCR/ABL t(9;22) Fusion is optimized to detect the t(9;22)(q34;q11) reciprocal translocation in a dual-color, dual-fusionassay on metaphase/interphase spreads, blood smears andbone marrow cells.This probe will also detect cryptic insertions of ABL into the BCRregion not detectable by karyotyping and therefore describedas Ph-negative.ON BCR/ABL t(9;22), TC, D-FusionThe BCR/ABL t(9;22), TC, D-Fusion probe is a triple-color, dualfusionprobe build from the same regions as the dual-color,dual-fusion probe, but the proximal BCR region is labeledin blue. Using the triple-color probe allows to distinguishbetween the derivative chromosome 22, the Philadelphiachromosome, which will be observed as purple (red/blue)color, while the derivative chromosome 9 will show a yellow(red/green) signal.Cat.# KBI-10005 BCR/ABL t(9;22), FusionCat.# KBI-10006 BCR/ABL t(9;22), TC, D-FusionSHGC-147754ASS340 KB22q11.2IGLC1D22S940340 KBSHGC-147754ASS340 KB22q11.2IGLC1D22S940340 KBABLABL1000 KB22BCR1000 KB22BCR9q34NUP214D9S1991IGLL11000 KB9q34NUP214D9S1991IGLL11000 KB9SHGC-1074509SHGC-107450BCR/ABL t(9;22) Fusion probe hybridized on patient materialshowing t(9;22) (q34;q11) reciprocal translocation (2RG1R1G).Image kindly provided by Monika Conchon, São PauloLiterature:Morris et al, 1990, Blood, 76: 1812-1818.Dewald et al, 1998, Blood, 91: 3357-3365.Kolomietz et al, 2001, Blood, 97; 3581-3588.Huntly et al, 2003, Blood, 102; 1160-1168.Tkachuk et al., 1990, Science 250, 559-562Ordering information Color Tests Cat#ON BCR/ABL t(9;22) Fusion red/green 10 KBI-10005ON BCR/ABL t(9;22) Fusion red/green 20 KBI-12005BCR/ABL t(9;22), TC, D-Fusion probe hybridized on patientmaterial showing translocation of distal BCR (1BG1RB1R1G).Image kindly provided by Prof Siebert, KielLiterature:Morris et al, 1990, Blood, 76: 1812-1818.Dewald et al, 1998, Blood, 91: 3357-3365.Kolomietz et al, 2001, Blood, 97; 3581-3588.Huntly et al, 2003, Blood, 102; 1160-1168.Tkachuk et al., 1990, Science 250, 559-562Ordering information Color Tests Cat#ON BCR/ABL t(9;22) TC, D-Fusion red/green/blue 10 KBI-10006Oncology Probes - Hematology Probes13

ON BCR/ABL t(9;22), DC, S-Fusion, ESA single-fusion assay is preferably used for the initial screeningof CML and ALL patients. By adding an additional regionproximal to the breakpoints on chromosome 9q34, this probewill provide an extra signal on the der(9q34) in case of at(9;22). The Philadelphia chromosome, der(22q), is visualizedby the fusion signal.ON BCR/ABL t(9;22), DC, S-FusionA simple dual-color, single-fusion assay is preferably used forthe initial screening of CML and ALL patients. The Philadelphiachromosome, der(22q), is visualized by a fusion signal whilethe der(9q) shows no signal.Cat.# KBI-10008 BCR/ABL t(9;22), Dual-Color, Single-Fusion,Extra SignalCat.# KBI-10009 BCR/ABL t(9;22) Dual-Color, Single-FusionSHGC-147754ASS340 KB22q11.2IGLC1D22S940340 KBSHGC-147754ASS22q11.2IGLC1D22S940340 KBABLABL1000 KB22BCR1000 KB22BCR9q34NUP214D9S1991IGLL19q34NUP214D9S1991IGLL19SHGC-1074509SHGC-107450Oncology Probes - Hematology Probes14BCR/ABL t(9;22), DC, S-Fusion, ES hybridized to a normalmetaphase (2R2G).Literature:Morris et al, 1990, Blood, 76: 1812-1818.Dewald et al, 1998, Blood, 91: 3357-3365.Kolomietz et al, 2001, Blood, 97; 3581-3588.Huntly et al, 2003, Blood, 102; 1160-1168.Tkachuk et al., 1990, Science 250, 559-562Ordering information Color Tests Cat#ON BCR/ABL t(9;22) DC, S-Fusion, ES red/green 10 KBI-10008BCR/ABL t(9;22), DC, S-Fusion hybridized to a normalmetaphase (2R2G).Literature:Morris et al, 1990, Blood, 76: 1812-1818.Dewald et al, 1998, Blood, 91: 3357-3365.Kolomietz et al, 2001, Blood, 97; 3581-3588.Huntly et al, 2003, Blood, 102; 1160-1168.Tkachuk et al., 1990, Science 250, 559-562Ordering information Color Tests Cat#ON BCR/ABL t(9;22) DC, S-Fusion red/green 10 KBI-10009

CML secondary chromosomal changesON p53 (17p13) / MPO (17q22) “ISO 17q”Isochromosome 17q is the most common isochromosomein cancer. It plays an important role in tumor developmentand progression. Hematologic malignancies such as chronicmyeloid leukemia (CML) with isochromosome 17q carry apoor prognosis. Isochromosome 17q is the most commonchromosome abnormality in primitive neuroectodermaltumors and medulloblastoma. Isochromosome 17q is, byconvention, symbolized as i(17q).The p53 (17p13) / MPO (17q22) “ISO 17q” probe is optimizedto detect copy numbers of the p53 gene region at 17p13 andMPO gene region at 17q22. In case of i(17q) a signal patternof three red signals for MPO (17q22) and one signal for p53at 17p13 is expected.SE 8 (D8Z1)SE 7 (D7Z1) / SE 8 (D8Z1)Gain of chromosome 8 is the most common secondarychromosomal aberration in CML (approx. 34%).Cat.# KBI-10011 p53 (17p13) / MPO (17q22) “ISO 17q”Cat.# KBI-20008 SE 8 (D8Z1)Cat.# KBI-20031 SE 7 (D7Z1) / SE 8 (D8Z1)D17S96017p13P53D17S634330 KB17q22D17S215117 MPO 400 KBSHGC-144222See description under Satellite Enumeration probeson page 84.p53 (17p13) / MPO (17q22) "ISO 17q" hybridized to a normalmetaphase (2R2G).Literature:Becher et al, 1990, Blood, 75: 1679-1683.Fioretos et al, 1999, Blood, 94: 225-232.Ordering information Color Tests Cat#ON p53 (17p13) / MPO (17q22) “ISO 17q” green/red 10 KBI-10011Ordering information Color Tests Cat#SE 8 (D8Z1) red/green 10 KBI-20008SE 7 (D7Z1) / SE 8 (D8Z1) red/green 10 KBI-20031Oncology Probes - Hematology Probes15

Other Myeloproliferative Diseases:ON FIP1L1-CHIC2-PDGFRA (4q12) Del, BreakIdiopathic hypereosinophilic syndrome (HES) and chroniceosinophilia leukemia (CEL) represent the most recent additionsto the list of molecularly defined chronic myeloproliferativedisorders. A novel tyrosine kinase that is generated from fusionof the Fip1-like 1 (FIP1L1) and PDGFRα (PDGFRA) genes hasbeen identified as a therapeutic target for imatinib mesylate inhypereosinophilic syndrome (HES). This fusion results from anapproximately 800-kb interstitial chromosomal deletion thatincludes the cysteine-rich hydrophobic domain 2 (CHIC2) locus.ON FIP1L1-CHIC2-PDGFRA (4q12) Del, Break, TCThe FIP1L1-CHIC2-PDGFRA triple-color probe is optimized todetect the CHIC2 deletion at 4q12 associated with the FIP1L1/PDGFRA fusion in a triple-color, split assay. It also allows thedetection of translocation involving the FIP1L1 and PDGFRAregion. The split of the green and blue signal will indicate atranslocation at 4q12 independent of a possible chromosome4 polyploidy.The FIP1L1-CHIC2-PDGFRA probe is optimized to detect theCHIC2 deletion at 4q12 associated with the FIP1L1/PDGFRAfusion in a Dual-Color, split assay. It also allows the detectionof translocation involving the FIP1L1 and PDGFRA region.However, chromosome 4 polyploidy may provide additionalsignals not associated with a translocation involving 4q12.Cat.# KBI-10003 FIP1L1-CHIC2-PDGFRA (4q12) Del, BreakCat.# KBI-10007 FIP1L1-CHIC2-PDGFRA (4q12) Del, Break, Triple-ColorRH 105779RH 105779FIP1L1RH 65011RH 454614q12CHIC2640 KB460 KBFIP1L1RH 65011RH 454614q12CHIC2640 KB460 KBRH 43339RH 43339PDGFRA300 KBPDGFRA300 KBRH 43290RH 43290Oncology Probes - Hematology Probes4FIP1L1-CHIC2-PDGFRA (4q12) Del, Break probe hybridized to anormal interphase/metaphase (2RG).Literature:Cools et al, N Engl J Med, 2003, 348, 1201-1214.Godlib et al, Blood, 2004, 103, 2879-2891.Ordering information Color Tests Cat#ON FIP1L1-CHIC2-PDGFRA (4q12) Del, Break red/green 10 KBI-100034FIP1L1-CHIC2-PDGFRA (4q12) Del, Break, TC probe hybridizedto a normal metaphase (2BRG).Literature:Cools et al, 2003, N Engl J Med, 348: 1201-1214.Griffin et al, 2003, PNAS, 100: 7830-7835.Gotlib et al, 2004, Blood, 103; 2879-2891.Ordering information Color Tests Cat#ON FIP1L1-CHIC2-PDGFRA (4q12) Del, Break, TC red/green/blue 10 KBI-1000716

ON PDGFRB (5q33) BreakPDGFRB activation has been observed in patients with chronicmyelomonocytic leukemia/atypical chronic myeloid leukemiaand has been associated with 11 translocation partners,the best known is the ETV6 or TEL gene on 12p13, causinga t(5;12) translocation. Cytogenetic responses are achievedwith imatinib in patients with PDGFRB fusion positive, BCR/ABL negative CMPDs.The PDGFRB probe is optimized to detect translocationsinvolving the PDGFRB region at 5q33 in a dual-color, splitassay.ON FGFR1 (8p12) BreakFGFR1 has been implicated in the tumorigenesis ofhaematological malignancies, where it is frequently involvedin balanced chromosomal translocations, including cases ofchronic myeloid leukaemia (BCR-FGFR1 fusion) and the 8p11myeloproliferative syndrome/stem cell leukaemia–lymphomasyndrome, which is characterized by myeloid hyperplasia andnon-Hodgkin’s lymphoma with chromosomal translocationsfusing several genes, the most common being a fusion betweenZNF198 and FGFR1.Cat.# KBI-10004 PDGFRB (5q33) BreakCat.# KBI-10737 FGFR1 (8p12) BreakD5S1907330 KBPDGFRB400 KB5q33.2D5S20145PDGFRB (5q33) Break probe hybridized to a normalmetaphase (2RG).Literature:Wlodarska et al, 1997, Blood, 89: 1716-1722.Wilkinson et al, 2003, Blood, 102: 4287-419Ordering information Color Tests Cat#ON PDGFRB (5q33) Break red/green 10 KBI-10004See description under Solid Tumors on page 49.Ordering information Color Tests Cat#FGFR1 (8p12) Break red/green 10 KBI-10737Oncology Probes - Hematology Probes17

Chronic Lymphocytic Leukemia (CLL)CLL accounts for about 30% of all leukemias inEurope and the USA. Distinct clonal chromosomalabnormalities can be identified in up to 90% ofCLL cases of the B-cell lineage. By FISH the mostcommon chromosomal changes in CLL and theirfrequencies have been identified as shown in thetable below.ON DLEU (13q14) / 13qterDeletions of chromosome 13q14 have been reported notonly in CLL but in a variety of human tumors, includingother types of lymphoid and myeloid tumors, as well asprostate, head and neck, and non-small cell lung cancers.The deletion of 13q may be limited to a single locus (13q14),or accompanied with the loss of a larger interstitial regionof the long arm of chromosome 13. A minimal critical regionof 400 kb has been described containing the DLEU1, DLEU2and RFP2 genes.The DLEU (13q14) specific DNA probe is optimized to detectcopy numbers of the DLEU gene region at 13q14. The13qter (13q34) region is included to facilitate chromosomeidentification.Del(13q14) 55%Del(11q) 18%Trisomy 12q 16%Del(17p) 7%Cat.# KBI-10102 DLEU (13q14) / 13qterRB1D13S147713q14 RFP2DLEU1D13S272650 KB220 KBDel(6q) 6%13q3413D13S25450 KBTrisomy 8q 5%t(14q32) 4%Trisomy 3q 3%Oncology Probes - Hematology ProbesDLEU (13q14) / 13qter probe hybridized to patient material showinga 13q14 deletion (1R2G).Image kindly provided by Dr. Dastugue, ToulouseLiterature:Wolf et al, 2001, Hum Mol Genet, 10: 1275-1285.Corcoran et al, 1998, Blood, 91: 1382-1390.Ordering information Color Tests Cat#ON DLEU (13q14) / 13qter red/green 10 KBI-1010218

ON p53 (17p13) / SE 17The p53 tumor suppressor gene at 17p13, has beenshown to be implicated in the control of normal cellularproliferation, differentiation, and apoptosis. Allelic loss,usually by deletion, and inactivation of p53 have beenreported in numerous tumor types and are associated withpoor prognosis in CLL.The p53 (17p13) specific DNA probe is optimized todetect copy numbers of the p53 gene region at 17p13. Thechromosome 17 satellite enumeration probe (SE 17) atD17Z1 is included to facilitate chromosome identification.ON ATM (11q22) / SE 11Chromosome 11q22.3-23.1 deletions involving the ataxiateleangiectasiamutated (ATM) locus are detected at diagnosisin 15-20% of cases of B-cell chronic lymphocytic leukemia(CLL) and are associated with a relatively aggressive disease.Loss of the 11q22-23 region, where the ataxia-telangiectasiamutated (ATM) gene is located is also one of the mostfrequent secondary chromosomal aberrations in mantle celllymphoma.The ATM (11q22.3) specific DNA probe is optimized to detectcopy numbers of the ATM gene region at region 11q22.3. Thechromosome 11 satellite enumeration (SE 11) at D11Z1 probeis included to facilitate chromosome identification.Cat.# KBI-10112 p53 (17p13) / SE 17Cat.# KBI-10103 ATM (11q22) / SE 1117p13D17Z1D17S960D11Z1D11S4485330 KB17P53D17S63411q22ATMRH 39918230 KB11p53 (17p13) / SE 17 probe hybridized to a normalmetaphase (2R2G).Literature:Amiel A et al, 1997, Cancer Gener.Cytogenet,, 97; 97-100Drach J et al, 1998, Blood, 92; 802-809Ordering information Color Tests Cat#ON p53 (17p13) / SE 17 red/green 10 KBI-10112ON p53 (17p13) / SE 17 red/green 20 KBI-12112ATM (11q22) / SE 11 hybridized to patient materialshowing a 11q22 deletion at the ATM gene regionobserved (1R2G).Image kindly provided by Dr Wenzel, BaselLiterature:Doehner et al, 1997, Blood, 89: 2516-2522.Bigoni et al, 1997, Leukemia, 11: 1933-1940.Ordering information Color Tests Cat#ON ATM (11q22) / SE 11 red/green 10 KBI-10103Oncology Probes - Hematology Probes19

ON hTERC (3q26) / 3q11Amplification of the 3q26-q27 has a high prevalence incervical, prostate, lung, and squamous cell carcinoma.This amplification can also be found to a lesser extentin CLL patients. The minimal region of amplification wasrefined within a 1- to 2-Mb genomic segment containingseveral potential cancer genes including hTERC, the humantelomerase RNA gene.The hTERC (3q26) specific DNA probe is optimized to detectcopy numbers of the hTERC gene region at region 3q26.The 3q11 region probe is included to facilitate chromosomeidentification.ON GLI (12q13) / SE 12Trisomy 12 is the most common numerical chromosomalaberration in patients with B-cell chronic lymphocytic leukemia(B-CLL). Partial trisomy 12 of the long arm of chromosome 12consistently includes a smaller region at 12q13-15 and hasbeen observed in CLL and several other tumors. A number ofloci located close to either MDM2 or CDK4/SAS, including thegenes GADD153, GLI, RAP1B, A2MR, and IFNG, were foundto be coamplified.The GLI (12q13) specific DNA probe is optimized to detectcopy numbers of the GLI gene region at region 12q13. Thechromosome 12 satellite enumeration probe (SE 12) D12Z3is included to facilitate chromosome identification.Cat.# KBI-10110 hTERC (3q26) / 3q11Cat.# KBI-10104 GLI (12q13) / SE 12D12Z3RH 10132012q13GLI270 KB3q11RH 75890RH179193q26.2 hTERCRH10606370 KB123hTERC (3q26) / 3q11 probe hybridized to a normal interphase/metaphase (2R2G).Literature:Arnold et al, 1996, Genes Chrom Cancer, 16: 46-54.Soder et al, 1997, Oncogene, 14: 1013-1021.Ordering information Color Tests Cat#ON hTERC (3q26) / 3q11 red/green 10 KBI-10110GLI (12q13) / SE 12 hybridized to patient material showingGLI (12q13) amplification (3R2G).Image kindly provided by Dr Wenzel, BaselLiterature:Merup et al, 1997, Eur J Haematol, 58: 174-180.Dierlamm et al., 1997, Genes Chrom Cancer, 20: 155-166.Ordering information Color Tests Cat#ON GLI (12q13) / SE 12 red/green 10 KBI-10104Oncology Probes - Hematology Probes21

Other relevant CLL probes:ON IGH (14q32) BreakCat.# KBI-10601 IGH (14q32) BreakSee description under Multiple Myeloma on page 39.Ordering information Color Tests Cat#ON IGH (14q32) Break red/green 10 KBI-10601Myelodysplastic Syndromes (MDS)The myelodysplastic syndromes (MDS) are aheterogeneous group of hematopoietic disorderscharacterized in most patients by peripheral bloodcytopenia with hypercellular bone marrow anddysplasia of the cellular elements. Cytogeneticstudies play a major role in confirmation ofdiagnosis and prediction of clinical outcome in MDS,and have contributed to the understanding of itspathogenesis. Clonal chromosomal abnormalitiesare detected by routine karyotyping techniquesin 40%–70% of cases of de novo MDS, and 95% ofcases of therapy-related MDS.SE 12 (D12Z3)Cat.# KBI-20012 SE 12 (D12Z3)See description under Satellite Enumeration probes on page 85.Ordering information Color Tests Cat#SE 12 (D12Z3) red/green 10 KBI-20012Oncology Probes - Hematology Probes24

ON hTERT (5p15) / 5q31The hTERT / 5q31 dual-color probe can be used to detectdeletions involving band 5q31 in MDS and AML.The 5q- specific DNA probe is optimized to detect copynumbers at the CDC25C/EGR1 gene region at 5q31. The hTERTgene region at 5p15 is included to facilitate chromosomeidentification.ON MDS 5q- (5q31; 5q33)The presence of del(5q), either as the sole karyotypicabnormality or as part of a more complex karyotype, hasdistinct clinical implications for myelodysplastic syndromes(MDS) and acute myeloid leukemia. Interstitial 5q deletions arethe most frequent chromosomal abnormalities in MDS and arepresent in 10% to 15% of MDS patients. Two different criticalregions are described, one at 5q31-q33 containing the CSF1Rand RPS14 gene regions ,characteristic for the ‘5q-‘ syndrome,and a more proximal located region at 5q13-q31 containingthe CDC25C and EGR1 gene regions.The 5q- specific DNA probe is optimized to detect copy numbersat the CDC25C/EGR1 gene region at 5q31 and the CSF1R/RPS14gene region at 5q33 simultaneously in a dual-color assay.Cat.# KBI-10208 hTERT (5p15) / 5q31Cat.# KBI-10209 MDS 5q- (5q31; 5q33)5p15.3RH48032D5S1981hTERTD5S2269190 KBCDC25CEGR1D5S597645 KB5q31.25RH480325q31.2CDC25CEGR1645 KB5D5S2618CSF1R5q33.1 RPS14D5S2014650 KBD5S597hTERT (5p15) / 5q31 probe hybridized to a normal interphase/metaphase (2R2G).Literature:Zhao et al, 1997, PNAS, 94; 6948-6053Horrigan et al, 2000, Blood, 95; 2372-2377Ordering information Color Tests Cat#ON hTERT (5p15) / 5q31 red/green 10 KBI-10208MDS 5q- (5q31; 5q33) probe hybridized to patient materialshowing a 5q33 deletion (1R2G).Image kindly provided by Dr Mohr, DresdenLiterature:Boultwood J e.a., Blood 2002; 99: 4638-4641Zhao N e.a., PNAS 1997; 94: 6948-6953Wang e.a., Haematologica 2008; 93: 994-1000Ebert BL e.a., Nature 2008: 451: 335-339Mohamedali A and Mufti GJ, Brit J Haematol 2008; 144: 157-168Ordering information Color Tests Cat#ON MDS 5q- (5q31; 5q33) red/green 10 KBI-10209Oncology Probes - Hematology Probes25

ON MDS 5q- (5q31; 5q33) / hTERT (5p15) TCThe 5q- specific DNA probe is optimized to detect copynumbers at the CDC25C/EGR1 gene region at 5q31 and theCSF1R/RPS14 gene region at 5q33 simultaneously in a dualcolorassay. The triple-color probe provides in addition to thetwo critical regions a control in blue targeting the hTERT generegion at 5p15.ON MDS 7q- (7q22; 7q35)Loss of a whole chromosome 7 or a deletion of the long arm,del(7q), are recurring abnormalities in malignant myeloiddiseases. Most deletions are interstitial and there are twodistinct deleted segments of 7q. The majority of patients haveproximal breakpoints in bands q11-22 and distal breakpointsin q31-36. The CCAAT displacement protein (CUTL1) generegion is located in the 7q22 critical region.The 7q- specific DNA probe is optimized to detect copynumber of 7q at 7q22 and at 7q35 simultaneously in a dualcolorassayCat.# KBI-10210 MDS 5q- (5q31; 5q33) / hTERT (5p15), Triple-ColorCat.# KBI-10202 MDS 7q- (7q22; 7q35)5p15D5S1981hTERT190 KBD5S2269CUTL1200 KBD7S740RH480327q22CDC25C5q31.2EGR1D5S597645 KB7q35D7S2419320 KB55q33.1D5S2618CSF1R7D7S688D7S2640650 KBRPS14D5S2014Oncology Probes - Hematology Probes26MDS 5q- (5q31; 5q33) / hTERT (5p15) probe hybridized to anormal metaphase (2R2G2B).Literature:Boultwood J e.a., Blood 2002; 99: 4638-4641Zhao N e.a., PNAS 1997; 94: 6948-6953Wang e.a., Haematologica 2008; 93: 994-1000Ebert BL e.a., Nature 2008: 451: 335-339Mohamedali A and Mufti GJ, Brit J Haematol 2008; 144: 157-168Ordering information Color Tests Cat#ON MDS 5q- (5q31; 5q33) / hTERT (5p15) TC red/green/blue 10 KBI-10210MDS 7q- (7q22; 7q35) hybridized to patient material showinga 7q35 deletion (1R2G).Image kindly provided by Prof Jauch, HeidelbergLiterature:LeBeau et al., 1996, Blood, 88: 1930-1935.Doehner et al, 1998, Blood, 92: 4031-4035.Ordering information Color Tests Cat#ON MDS 7q- (7q22; 7q35) red/green 10 KBI-10202

ON MDS 7q- (7q22; 7q35) / SE 7 TCThe 7q- specific DNA probe is optimized to detect copynumber of 7q at 7q22 and at 7q35 simultaneously in a dualcolorassay.The chromosome 7 satellite enumeration probe (SE 7) at D7Z1in blue is included to facilitate chromosome identification.ON MDS 20q- (PTPRT 20q12) / 20q11Acquired deletions of the long arm of chromosome 20 arefound in several hematologic conditions and particularly inthe myeloproliferative disorders (MPD) and myelodysplasticsyndromes and acute myeloid leukemia (MDS/AML). A minimalcritical region deleted in MPD and MDS has been identifiedat 20q12 which includes a protein tyrosine phosphatasereceptor gene (PTPRT).The 20q- (PTPRT, 20q12) specific DNA probe is optimizedto detect copy numbers of 20q at region 20q12. A 20q11region specific probe is included to facilitate chromosomeidentification.Cat.# KBI-10207 MDS 7q (7q22; 7q35) / SE 7, Triple-ColorCat.# KBI-10203 MDS 20q- (PTPRT 20q12) / 20q11D7Z1ControlSHGC-144070MAPRE1600 KB20q11.21CUTL1200 KBRH574677q22D7S74020q1220D20S108360 KB77q35D7S2419D20S499PTPRT320 KBD7S688D7S2640MDS 7q (7q22; 7q35) / SE 7 TC probe hybridized to anormal metaphase (2R2G2B).Literature:LeBeau et al., 1996, Blood, 88: 1930-1935.Doehner et al, 1998, Blood, 92: 4031-4035.Ordering information Color Tests Cat#ON MDS 7q- (7q22; 7q35) / SE7 TC red/green/blue 10 KBI-10207MDS 20q- (PTPRT 20q12) / 20q11 probe hybridized to anormal metaphase (2R2G).Literature:Bench et al, 2000, Oncogene, 19: 3902-3913.Asimakopoulos et al, 1994, Blood, 84: 3086-3094.Ordering information Color Tests Cat#ON 20q- (PTPRT 20q12) / 20q11 red/green 10 KBI-10203Oncology Probes - Hematology Probes27

ON EVI t(3;3); inv(3) (3q26) BreakThe inv(3)(q21;q26) is a recurrent cytogenetic aberration ofmyeloid malignancy associated with fusion of EVI1 and RPN1and a poor disease prognosis. Genomic breakpoints in 3q26 areusually located proximal to the EVI1 locus, spanning a regionof several hundred kilobases. Other recurrent and sporadicrearrangements of 3q26 also cause transcriptional activationof EVI1 including the translocations t(3;3)(q21;q26) and t(3;21)(q26;q22). Breakpoints in the latter rearrangements spana wider genomic region of over 1 megabase encompassingsequences distal to EVI1 and neighboring gene MDS1.ON EVI t(3;3); inv(3), EVI (3q26) Break, TCThe EVI t(3;3) inv(3) Break, triple-color probe is optimized todetect the inversion of chromosome 3 involving the EVI generegion at 3q26 in a dual-color, split assay on metaphase/interphase spreads, blood smears and bone marrow cells. Byusing a third color breakpoint variations can now be easilydiscovered.The EVI t(3;3) inv(3) Break, dual-color probe is optimized todetect the inversion of chromosome 3 involving the EVI1gene region at 3q26 in a dual-color, split assay on metaphase/interphase spreads, blood smears and bone marrow cells.Cat.# KBI-10204 EVI t(3;3); inv(3) (3q26) BreakCat.# KBI-10205 EVI t(3;3); inv(3) (3q26), Triple-ColorRH103072420 KBD3S1243460 KBEVI1hTERC370 KBEVI1RH10606hTERC3q26.2370 KB3q26.2550 KBRH1060633RH123089Oncology Probes - Hematology ProbesEVI t(3;3);inv(3) (3q26) Break probe hybridized to patientmaterial showing a rearrangement involving the EVI gene regionat 3q26 (1RG1R1G).Image kindly provided by Dr. Reed, LondonLiterature:Levy et al, 1994, Blood, 83: 1348-1354.Wieser et al, 2003, Haematologica, 88: 25-30.Melo et al, 2007, Leukemia, 22, 434-437.Ordering information Color Tests Cat#ON EVI t(3;3); inv(3) (3q26) Break red/green 10 KBI-10204EVI t(3;3); inv(3) (3q26) TC probe hybridized to patientmaterial showing a rearrangement involving the EVI gene regionat 3q26 (1RGB1B1RG).Image kindly provided by Prof Jauch, HeidelbergLiterature:Levy et al, 1994, Blood, 83: 1348-1354.Wieser et al, 2003, Haematologica, 88: 25-30.Melo et al, 2007, Leukemia, 22, 434-437.Ordering information Color Tests Cat#ON EVI t(3;3); inv(3) (3q26) Break, TC red/green/blue 10 KBI-1020528Note: In t(3;3) the breakpoint cluster can span 1.3 Mb region. The described probe set willtherefore provide false negative results in cases with very distal breakpoints.

Acute Myeloid Leukemia (AML)At least 80% of patients with acute myeloid leukemia(AML) have an abnormal karyotype. Cytogeneticanalysis provides some of the strongest prognosticinformation available, predicting outcome of bothremission induction and postremission therapy.Abnormalities which indicate a good prognosisinclude t(8;21), inv(16), and t(15;17). Patients withAML that is characterized by deletions of the longarms or monosomies of chromosomes 5 or 7; bytranslocations or inversions of chromosome 3,t(6;9), t(9;22); or by abnormalities of chromosome11q23 have particularly poor prognoses withchemotherapy.ON AML/ETO t(8;21) Fusiont(8;21)(q22;q22) is the most frequently observed karyotypicabnormality associated with acute myeloid leukemia (AML),especially in FAB M2. As a consequence of the translocationthe AML1 (CBFA2, RUNX1) gene in the 21q22 region isfused to the ETO (MTG8 , RUNX1T) gene in the 8q22 region,resulting in one transcriptionally active gene on the 8qderivativechromosome.The AML/ETO t(8;21)(q21;q22) specific DNA probe is optimizedto detect the reciprocal translocation t(8;21) in a dual-color,dual-fusion assay.Cat.# KBI-10301 AML/ETO t(8;21) FusionRH 120950D21S325490 KB21q22.1570 KBRUNX1T(ETO)8q21.321RUNX1(AML1)600 KB600 KBRH 43237W 10808AMl/ETO t(8;21) Fusion probe hybridized to a normalmetaphase (2R2G).Literature:Sacchi et al, 1995, Genes Chrom Cancer, 79: 97-103.Hagemeijer et al, 1998, Leukemia, 12: 96-101.Ordering information Color Tests Cat#ON AML/ETO t(8;21) Fusion red/green 10 KBI-10301Oncology Probes - Hematology Probes29

ON PML/RARA t(15;17) FusionA structural rearrangement involving chromosomes 15 and 17in acute promyelocytic leukemia (APL) was first recognized in1977. The critical junction is located on the der(15) chromosomeand consists of the 5’ portion of PML fused to virtually all ofthe RARA gene. The PML/RARA fusion protein interacts witha complex of molecules known as nuclear co-repressors andhistone deacetylase. This complex binds to the fusion proteinand blocks the transcription of target genes. Other less commonvariant translocations fuse the RARA gene on 17q21 to thePLZF, NPM, NUMA, and STAT5b genes, respectively.The PML/RARA t(15;17) specific DNA probe is optimized todetect the reciprocal translocation t(15;17) (q24;q21) in a dualcolor,dual-fusion assay.ON MLL (11q23) BreakThe human chromosome band 11q23 is associated with a highnumber of recurrent chromosomal abnormalities includingtranslocations, insertions, and deletions. It is involved inover 20% of acute leukemias. The MLL (Myeloid-LymphoidLeukemia or Mixed-Lineage Leukemia) gene, named forits involvement in myeloid (usually monoblastic) andlymphoblastic leukemia, and less commonly in lymphoma islocated in the 11q23 breakpoint region. Leukemias involvingthe MLL gene usually have a poor prognosis.The MLL (11q23) break probe is optimized to detecttranslocations involving the MLL gene region at 11q23 in adual-color split assay.Cat.# KBI-10302 PML/RARA t(15,17) FusionCat.# KBI-10303 MLL (11q23) BreakRH 54241D17S2189D11S97615PML15q24D15S991420 KB300 KB1717q21RARARH 69878460 KBMLL (88KB)11q23D11S4538220 KB290 KB11Oncology Probes - Hematology ProbesPML/RARA t(15,17) Fusion probe hybridized to a normalmetaphase (2R2G).Literature:Schad et al, 1994, Mayo Clin Proc, 69: 1047-1053.Brockman et al, 2003, Cancer Genet Cytogenet, 145: 144-151.Ordering information Color Tests Cat#ON PML/RARA t(15,17) Fusion red/green 10 KBI-10302ON PML/RARA t(15,17) Fusion red/green 20 KBI-12302MLL (11q23) Break probe hybridized to patient materialshowing a translocation at 11q23 (1RG1R1G).Literature:Kobayashi et al, 1993, Blood, 81: 3027-3022Martinez-Climent et al, 1995, Leukemia, 9: 1299-1304.Ordering information Color Tests Cat#ON MLL (11q23) Break red/green 10 KBI-1030330

ON RARA (17q21) BreakThis break apart probe can detect the numerous types ofrecurrent rearrangement of the RARα (Retinoid acid receptor,alpha) gene with various gene partners (e.g., PML, NPM,MLL, FIP1L1, NuMA1, PLZF, amongst the others), leadingto the formation of different reciprocal fusion proteins. Theimportance of retinoid metabolism in acute promyelocyticleukemia (APL) is highlighted by the numerous recent studies,but the different leukemogenic functions of the RARα fusionproteins in the neoplastic myeloid development still has tobe defined, as well as the distinct clinical outcome of thepatients with the variant forms of APL.ON CBFB t(16;16); inv(16) BreakInv(16)(p13;q22) and t(16;16)(p13;q22) are recurringchromosomal rearrangements in AML. In both the inversionand translocation, the critical genetic event is the fusion ofthe CBFB gene at 16q22 to the smooth muscle myosin heavychain (MYH11) at 16p13. A deletion of between 150 and350 kb centromeric to the p-arm inversion breakpoint clusterregion can be observed in some patients containing the 5’portion of the myosin heavy chain (MYH11) gene.The CBFB t(16;16) inv(16) break probe is optimized to detectthe inversion of chromosome 16 involving the CBFB generegion at 16q22 in a dual-color, split assay.Cat.# KBI-10305 RARA (17q21) BreakCat.# KBI-10304 CBFB t(16;16); inv(16) BreakD17S214717q21RARA530 KBRH113713CBFB275 KB17D17S1196610 KB1616q22RH32600335 KBRARA (17q21) Break probe hybridized to patient materialshowing a translocation at 17q21 (1RG1R1G).Ordering information Color Tests Cat#ON RARA (17q21) Break red/green 10 KBI-10305CBFB t(16;16); inv(16) Break probe hybridized to a normalmetaphase (2RG).Literature:Dauwerse et al, 1993, Hum.Mol.Genet., 2: 1527-1534.Marlton et al, 1995, Blood, 85: 772-779.Ordering information Color Tests Cat#ON CBFB t(16;16); inv(16) Break red/green 10 KBI-10304Oncology Probes - Hematology Probes31

Acute Lymphoblastic Leukemia (ALL)Acute lymphocytic leukemia, also called acutelymphoblastic leukemia, is a type of cancer thatstarts from white blood cells in the bone marrow. Anumber of recurring cytogenetic abnormalities areassociated with distinct immunologic phenotypesof ALL and characteristic outcomes. The ETV6/AML1fusion arising from the translocation t(12;21)(p13;q22)has been associated with a good outcome; the BCR/ABL fusion of t(9;22)(q34;q11), rearrangements of theMLL gene (11q23), and abnormalities of the short armof chromosomes 9 involving the tumor suppressorgenes p16 (INK4A) have a poor prognosis.ON TEL/AML t(12;21) FusionThe t(12;21), a cryptic translocation rarely observed byconventional cytogenetics, was first identified by fluorescencein situ hybridization (FISH). In ALL blasts, this translocationfuses the 5’ part of the TEL (ETV6) gene with almost the entireAML1 (CBFA2) gene, producing the chimeric transcript ETV6-CBFA2. The t(12;21) (p13;q22) has also been identified as themost frequent chromosomal abnormality in childhood ALL,affecting 20% to 25% of B-lineage cases.The TEL/AML t(12;21) specific DNA probe is optimized todetect the reciprocal translocation t(12;21) (p13;q22) in adual-color, dual-fusion assay.Cat.# KBI-10401 TEL/AML t(12;21) Fusion12p13.2RH 39900D21S325490 KB21q22.1570 KBETV6(TEL)21RUNX1(AML1)RH 76656360 KBRH 43237600 KB12Oncology Probes - Hematology ProbesTEL/AML t(12;21) Fusion probe hybridized to a normalmetaphase (2R2G).Literature:Romana et al, 1995, Blood, 85: 3662-3670.Ordering information Color Tests Cat#ON TEL/AML t(12;21) Fusion red/green 10 KBI-1040132

ON ETV6 (TEL) (12p13) BreakETV6 (TEL) gene is the abbreviation for -ETS variant 6-gene. It encodes an ETS family factor which functions as atranscriptional repressor in hematopoiesis and in vasculardevelopment. The gene is located on chromosome 12p13, andis frequently rearranged in human leukemias of myeloid orlymphoid origins. Also systematic deletion of the normal ETV6allele in patients with ETV6-AML1 fusions can be found.ON p16 (9p21) / 9q21Hemizygous deletions and rearrangements of chromosome9, band p21, are among the most frequent cytogeneticabnormalities detected in pediatric acute lymphoblasticleukemia (ALL). This deletion includes loss of the p16 (INK4A)/p15 (INK4B) genes, which are cell cycle kinase inhibitors andimportant in leukemogenesis.The p16 (9p21) specific DNA probe is optimized to detectcopy numbers of the p16 (INK4A) gene region at region 9p21.The 9q21 region probe is included to facilitate chromosomeidentification.Cat.# KBI-10403 ETV6 (TEL) (12p13) BreakCat.# KBI-10402 p16 (9p21) / 9q21RH 7797212p13495 KB9p21D9S1749ETV6D12S922545 KB9q21p16p15D9S975400 KB129ETV6 (TEL) (12p13) Break probe hybridized to patientmaterial showing a translocation involving the ETV6 regionat 12p13 (1RG1R1G).Image kindly provided by Magret Ratjen, KielLiterature:Golub et al, 1995, PNAS 92; 4917-4921Ford et al, 2001, Blood 98; 558-564Ordering information Color Tests Cat#ON ETV6 (TEL) (12p13) Break red/green 10 KBI-10403p16 (9p21) / 9q21 hybridized on patient material showingan isochromosome 9.Image kindly provided by Dr Wenzel, BaselLiterature:Dreyling et al, 1995, Blood, 86: 1931-1938.Southgate et al, 1995, Br J Cancer, 72: 1214-1218.Ordering information Color Tests Cat#ON p16 (9p21) / 9q21 red/green 10 KBI-10402Oncology Probes - Hematology Probes33

ON MLL (11q23) BreakCat.# KBI-10303 MLL (11q23)See description under AML on page 30.Ordering information Color Tests Cat#ON MLL (11q23) Break red/green 10 KBI-10303Multiple Myeloma (MM)The cytogenetic picture in multiple myeloma(MM) is highly complex, from which non-randomnumerical and structural chromosomal changeshave been identified. Specifically, translocationsinvolving the immunoglobulin heavy chain gene(IGH) at 14q32 and either monosomy or deletionsof chromosome 13 have been observed in asignificant number of patients. More recentlyseveral additional deletions or amplificationshave been identified in MM which are currentlyinvestigated in large patient studies.Note: Multiple Myeloma is a cancer of plasma cells. Analysisof such cells is hampered by their low frequency. Enrichmentof plasma cells using CD138 is highly recommended.ON BCR/ABL t(9;22)The t(9;22) BCR/ABL translocation is present in about 5% ofpediatric and up to 50% of adult ALL cases, and is associatedwith poor prognosis.Cat.# KBI-10005 ON BCR/ABL t(9;22) FusionCat.# KBI-12005 ON BCR/ABL t(9;22) FusionCat.# KBI-10006 ON BCR/ABL t(9;22) TC, D-FusionCat.# KBI-10008 ON BCR/ABL t(9;22) DC, S-Fusion, ESCat.# KBI-10009 ON BCR/ABL t(9;22) DC, S-FusionSee description under CML on page 13 and 14.Oncology Probes - Hematology ProbesOrdering information Color Tests Cat#ON BCR/ABL t(9;22) Fusion red/green 10 KBI-10005ON BCR/ABL t(9;22) Fusion red/green 20 KBI-12005ON BCR/ABL t(9;22) TC, D-Fusion red/green/blue 10 KBI-10006ON BCR/ABL t(9;22) DC, S-Fusion, ES red/green 10 KBI-10008ON BCR/ABL t(9;22) DC, S-Fusion red/green 10 KBI-1000934

ON MM 1q21 / 8p21Amplifications of 1q21 are concurrent with dysregulatedexpression of c-MAF, MMSET/FGFR3, or Del13 and representan independent unfavorable prognostic factor. Allelic lossesof the chromosome 8p21-22 have been reported as a frequentevent in several cancers.The 1q21 specific DNA probe is optimized to detect copynumbers at 1q21. The 8p21 specific DNA region is optimizedto detect copy numbers at 8p21.ON MM 19q13 / p53 (17p13)P53 gene deletion, which can be identified by interphaseFISH in almost a third of patients with newly diagnosed MM,is a novel prognostic factor predicting for short survival ofMM patients treated with conventional-dose chemotherapy.Amplification of 19q13 has been reported in a variety ofcancer.The 19q13 specific DNA probe is optimized to detect copynumbers at 19q13. The p53 (17p13) specific DNA region isoptimized to detect copy numbers of the p53 gene region at17p13.Cat.# KBI-10503 MM 1q21 / 8p21Cat.# KBI-10509 MM 19q13 / p53 (17p13)8p21.1WI-1821RH1443317p13D1S1953EPNOCRH81368205 KB19CD3719q13.3RH20642340 KB17D17S960P53D17S634330 KB1q21S100A10330 KB8SHGC-1447401MM 1q21 / 8p21 hybridized to a normal metaphase (2R2G).Literature:Shaughnessy J., 2005, Hematology, 10 suppl 1: 117-126.Cremer et al, 2005, Genes Chrom Cancer, 44: 194-203.Ordering information Color Tests Cat#ON MM 1q21 / 8p21 red/green 10 KBI-10503MM 19q13 / p53 (17p13) hybridized to patient material showinga p53 (17p13) deletion (1R2G).Image kindly provided by Prof Jauch, HeidelbergLiterature:Drach et al, 1998, Blood, 92: 802-809.Cremer et al, 2005, Genes Chrom Cancer, 44: 194-203.Ordering information Color Tests Cat#ON MM 19q13 / p53 (17p13) red/green 10 KBI-10509Oncology Probes - Hematology Probes37

ON MM 15q22 / 6q21Chromosome 6q amplifications encompassing 6q21-22have been observed in MM including the same region as inCLL. Amplification including band 15q22 has been reportedin MM.The 15q22 specific DNA probe is optimized to detect copynumbers at 15q22. The 6q21 specific DNA region is optimizedto detect copy numbers at 6q21.ON MM 15q22 / 9q34The hyperdiploid subtype in MM is defined by presenceof multiple trisomic chromosomes. Combination of thechromosome 9q34 and 15q22 specific regions are importantprobe to recognize the hyperdiploid subtype in MMwhich is usually associated with a low frequency of IGHtranslocations.The 15q22 and 9q34 probe is designed as a dual-color assayto detect amplifications at 15q22 and 9q34.Cat.# KBI-10504 MM 15q22 / 6q21Cat.# KBI-10508 MM 15q22 / 9q34SHGC-147754D15S534ASS340 KBD15S534RH 99154SEC63275 KB15q22.3SMAD6540 KBABL15q22.3SMAD6540 KB6q21D6S24615SHGC-1545199q34NUP214D9S199115SHGC-15451996Oncology Probes - Hematology ProbesMM 15q22 / 6q21 hybridized to MM patient material withamplification of both critical regions 6q21 and 15q22.Image kindly provided by Prof Jauch, HeidelbergLiterature:Cremer et al, 2005,Genes Chrom Cancer, 44: 194-203.Ordering information Color Tests Cat#ON MM 15q22 / 6q21 red/green 10 KBI-10504MM 15q22 / 9q34 hybridized to a normal interphase/metaphase (2R2G)Literature:Cremer et al, 2005,Genes Chrom Cancer, 44: 194-203.Ordering information Color Tests Cat#ON MM 15q22 / 9q34 red/green 10 KBI-1050838

ON MM 1q21 / SRD (1p36)Frequent loss of heterozygosity (LOH) on the short arm ofchromosome 1 (1p) has been reported in a series of humanmalignancies. The combination with the potentially amplified1q21 region allows to detect deletions at 1p36 and gain of1q21 in a single FISH assay.The 1q21 specific DNA probe is optimized to detect copynumbers at 1q21. The SRD 1p36 specific DNA Probe isoptimized to detect copy numbers of 1p at region 1p36containing the markers D1S2795 and D1S253.ON IGH (14q32) BreakMultiple myeloma is characterized by complex rearrangementsinvolving the IgH gene, particularly at the constant locus. TheIgH rearrangement provides a useful marker of clonality inB-cell malignancies and amplification of this rearrangementis the method of choice to monitor the residual tumor cellsin multiple myeloma.The IGH (14q32) break probe is optimized to detecttranslocations involving the IGH gene region at 14q32 in adual-color, split assay.Cat.# KBI-10507 MM 1q21 / SRD (1p36)Cat.# KBI-10601 IGH (14q32) Break1p36.3D1S2795SHGC-149299CHD5D1S286E530 KBD1S2531q21D1S1953ES100A10330 KB1SHGC-144740See description under Lymphoma on page 42.MM 1q21 / SRD (1p36) hybridized to a normalmetaphase (2R2G).Literature:Cremer et al, 2005, Genes Chrom Cancer, 44: 194-203.Shaughnessy J., 2005, Hematology, 10 suppl 1: 117-126.Ordering information Color Tests Cat#ON 1q21 / SRD (1p36) red/green 10 KBI-10507Literature:Taniwaki et al, 1994, Blood, 83: 2962-1969.Moreau et al, 2002, Blood, 100: 1579-1583.Ordering information Color Tests Cat#ON IGH (14q32) Break red/green 10 KBI-10601Oncology Probes - Hematology Probes39

ON BCL1/IGH t(11;14) FusionMantle cell lymphoma is a subtype of non-Hodgkin lymphomacharacterized by poor prognosis. Cytogenetically t(11;14)is associated with 75% of mantle cells lymphomas. Thetranslocation breakpoints are scattered within the 120 kbBCL1 region adjacent to CCND1. The translocation leads tooverexpression of cyclin D1 due to juxtaposition of the Igheavy chain gene enhancer on 14q32 to the cyclin D1 geneon 11q13.The BCL1/IGH t(11;14)(q13;q32) specific DNA probe isoptimized to detect the reciprocal translocation t(11;14) ina dual-color, dual-fusion assay.ON BCL2/IGH t(14;18) FusionThe t(14;18) chromosomal translocation that results in thejuxtaposition of the BCL2 proto-oncogene with the heavychain JH locus. It a common cytogenetic abnormality inhuman lymphoma and is observed in about 85% of follicularlymphoma (FL) and up to one-third of diffuse lymphomas(DL). Two breakpoint regions cluster , major breakpointregion (mbr) within the 3’ untranslated region of the BCL2proto-oncogene accounts for approximately 60% of thecases and the minor cluster region (mcr) 30 kb 3’ of BCL2accounts for approximately 25% of the breakpoints.The BCL2/IGH t(14;18)(q21;q32) specific DNA probe isoptimized to detect the reciprocal translocation t(18;14) ina dual-color, dual-fusion assay.Cat.# KBI-10604 BCL1/IGH t(11;14) FusionCat.# KBI-10606 BCL2/IGH t(14;18) FusionRH 52377D14S683EJAG2D14S683EJAG2RH750601111q13MYEOVCCND1RH 67810FGF4FGF3RH 48109510 KB660 KB14IGHCIGHJIGHD14q32IGHVD14S308600 KB600 KB14IGHCIGHJIGHD14q32IGHVD14S308600 KB600 KB18BCL218q21RH 13770535 KB540 KBBCL1/IGH t(11;14) Fusion probe hybridized to a normal interphase/metaphase (2R2G).Literature:Vaandrager et al, 1996, Blood, 88: 1177-1182.Ordering information Color Tests Cat#ON BCL1/IGH t(11;14) Fusion red/green 10 KBI-10604BCL2/IGH t(14;18) probe hybridized to a normal interphase/metaphase (2R2G).Literature:Poetsch et al, 1996, J Clin Oncol, 14: 963-969.Vaandrager et al, 2000, Genes Chrom Cancer, 27: 85-94.Ordering information Color Tests Cat#ON BCL2/IGH t(14;18) Fusion red/green 10 KBI-10606Oncology Probes - Hematology Probes41

ON IGH (14q32) BreakChromosomal rearrangements involving the immunoglobulinheavy chain gene (IGH) at 14q32 are observed in 50% ofpatients with B-cell non-Hodgkin’s lymphoma (NHL) andmany other types of Lymphomas. More than 50 translocationpartners with IGH have been described. In particular t(8;14),is associated with Burkitt’s lymphoma, t(11;14) is associatedwith Mantle cell lymphoma, t(14;18) is observed in a highproportion of follicular lymphomas and t(3;14) is associatedwith Diffuse Large B-Cell Lymphoma.The IGH (14q32) break probe is optimized to detecttranslocations involving the IGH gene region at 14q32 in adual-color, split assay. Kreatech has developed this probe forthe specific use on cell material (KBI-10601), or for the useon tissue (KBI-10729).ON MALT (18q21) BreakLow grade malignant lymphomas arising from mucosaassociated lymphoid tissue (MALT) represent a distinctclinicopathological entity. The three major translocationsseen in MALT lymphomas are t(11;18)(q21;q21)/API2-MALT1,t(14;18)(q32;q21)/IGH-MALT1 and t(1;14)(p22;q32)/IGH-BCL10. A break or split probe for MALT (18q21) is best usedto analyze translocation of the MALT gene on formalin fixedparaffin embedded tissue for routine clinical diagnosis.Kreatech has developed this probe for the specific use on cellmaterial (KBI-10608), or for the use on tissue (KBI-10731).Cat.# KBI-10601 IGH (14q32) BreakCat.# KBI-10608 MALT (18q21) BreakD18S1055D14S683EJAG2345 KBIGHCIGHJIGHD14q32600 KB1818q21 MALTRH103885680 KB14IGHV400 KBD14S308Oncology Probes - Hematology ProbesIGH (14q32) Break probe hybridized to patient material showing apartial deletion of 14q32 (1RG1R).Literature:Taniwaki et al, 1994, Blood, 83: 2962-1969.Gozetti et al, 2002, Cancer Research, 62: 5523-5527.Ordering information Color Tests Cat#ON IGH (14q32) Break red/green 10 KBI-10601MALT (18q21) Break probe hybridized to patient material showing atranslocation at 18q21 (1RG1RG).Literature:Morgan et al, 1999, Cancer Res, 59; 6205-6213Dierlamm et al, 2000, Blood, 96; 2215-2218.Ordering information Color Tests Cat#ON MALT (18q21) Break red/green 10 KBI-1060842

ON CCND1 (BCL1;11q13) BreakBesides the important functions in cellular growth,metabolism, and cellular differentiation, CCND1 (also knownas Cyclin D1 or BCL1) can also function as a proto-oncogene,often dysregulated after re-arrangement by translocation. Infact, it can juxtapose into many different gene locus to drivetumorigenic effects. To date, the gene has been found to berearranged in leukemias, in multiple myelomas (MM), and insome cases of benign parathyroid tumors. More specifically,the chromosomal translocation t(11;14)(q13:q32), involvingrearrangement of the CCND1 locus, has been reported to beassociated with human lymphoid neoplasia affecting mantlecell lymphomas (MCL).The rearrangement has been documented in 40-70% ofcases of mantle cell lymphoma, whereas it only rarely occursin other B cell lymphomas. In multiple myeloma, the sametranslocation t(11;14)(q13:q32) is the most common, witha reported frequency of 15% to 20% of the cases. For thisreason, the CCND1 break apart probe KBI-10609 can beconsidered a very useful tool for routine diagnosis in MCLand Multiple myeloma, to be used in association to therelated probes KBI-10604 and KBI-10605 probes that candetect more specifically the translocation t(11;14) in MantleCell Lymphoma (KBI-10604) and Multiple Myeloma (KBI-10605).Cat.# KBI-10609 CCND1 (BCL1; 11q13) BreakD11S1267630 KB11q13MYEOVGap 440 KB11CCND1510 KBD11S3652CCND1 (BCL1; 11q13) Break probe hybridized to a normalmetaphase (2R2G).Literature:Vaandrager et al, 1996, Blood, 88 (4); 1177-1182Vaandrager et al, 1997, Blood, 89; 349-350Ordering information Color Tests Cat#ON CCND1 (BCL1;11q13) Break red/green 10 KBI-10609Oncology Probes - Hematology Probes43

ON BCL6 (3q27) BreakChromosomal translocations involving band 3q27 withvarious different partner chromosomes represent a recurrentcytogenetic abnormality in B-cell non-Hodgkin’s lymphoma.A FISH strategy using two differently labeled flanking BCL6probes provides a robust, sensitive, and reproducible methodfor the detection of common and uncommon abnormalities ofBCL6 gene in interphase nuclei. Kreatech has developed thisprobe for the specific use on cell material (KBI-10607), or forthe use on tissue (KBI-10730).Note: Two different breakpoint regions have been identified,the major breakpoint region (MBR) is located within the5’ noncoding region of the BCL6 proto-oncogene, while theatypical breakpoint region (ABR) is located approximately250 kb proximal to the BCL6 gene. The Poseidon BCL6 (3q27)is designed in a way to flank both possible breakpoints,thereby providing clear split signals in either case.ON MYC (8q24) Break, TCRearrangements of the protooncogene C-myc (or MYC) havebeen consistently found in tumor cells of patients sufferingfrom Burkitt’s lymphoma. In cases with the common t (8;14)chromosomal translocation, the c-myc gene is translocatedto chromosome 14 and rearranged with the immunoglobulinheavychain genes; the breakpoint occurs 5’ to the c-mycgene and may disrupt the gene itself separating part ofthe first untranslated exon from the remaining two codingexons. In Burkitt’s lymphoma showing the variant t (2;8)or t (8;22) translocations, the genes coding for the k and lmmunoglobulin light chain are translocated to chromosome8. The rearrangement takes place 3’ to the c-myc gene. At thepresent time the mechanism by which the oncogenic potentialof the c-myc gene may be activated by these rearrangementsis still controversial.The MYC (8q24) break-apart probe is optimized to detectrearrangements involving the 8q24 locus in a triple-color, splitassay on metaphase/interphase spreads, blood smears andbone marrow cells.Cat.# KBI-10607 BCL6 (3q27)Cat.# KBI-10611 MYC (8q24) Break, TCD8S1813D3S4060550 KB878 KBRH77966D8S1017BCL6ABR*MBR*MYC740 KB350 KB8q24RH750253q27D3S32458D8S1128866 KBOncology Probes - Hematology Probes443ABR* atypical breakpoint regionMBR* major breakpoint regionBCL6 (3q27) Break probe hybridized to patient material (1RG1R1G).Image kindly provided by Prof Siebert, KielLiterature:Butler et al, 2002, Cancer Res, 62; 4089-4094.Sanchez-Izquierdo, 2001, Leukemia, 15; 1475-1484.Ordering information Color Tests Cat#ON BCL6 (3q27) Break red/green 10 KBI-10607SHG 172475MYC (8q24) Break probe hybridized to patient material showing a8q24 proximal break (1GBR1G1BR).Image kindly provided by Prof. Siebert, Kiel.Literature:Fabris et al, 2003, Genes Chromosomes Cancer 37 ; 261-269Hummel et al., 2006, N Engl J Med 354 ;2419-30.Ordering information Color Tests Cat#ON MYC (8q24) Break, TC red/green 10 KBI-10611

ON FGFR3/IGH t(4;14) FusionCat.# KBI-10602 FGFR3/IGH t(4;14) FusionSee description under Multiple Myeloma on page 36.Ordering information Color Tests Cat#ON FGFR3/IGH t(4;14) Fusion red/green 10 KBI-10602ON MYEOV/IGH t(11;14) FusionCat.# KBI-10605 MYEOV/IGH t(11;14) FusionSee description under Multiple Myeloma on page 35.Ordering information Color Tests Cat#ON MYEOV/IGH t(11;14) Fusion red/green 10 KBI-10605Oncology Probes - Hematology Probes45

Oncology probes - Solid TumorsIn solid tumors significantly high levels of chromosome abnormalities have been detected, but distinctionbetween significant and irrelevant events has been a major challenge. Consequently, the application ofcytogenetic technology as diagnostic, prognostic, or therapeutic tools for these malignancies has remainedlargely underappreciated. The emergence of FISH is particularly useful for solid malignancies, and thespectrum of their application is rapidly expanding to improve efficiency and sensitivity in cancer diagnosis,prognosis, and therapy selection, alone or with other diagnostic methods.Description Cat# PageDescription Cat# PageON ERBB2, Her-2/Neu (17q12) / SE 17 KBI-10701 47ON EGFR, Her-1 (7p11) / SE 7 KBI-10702 59ON CC hTERC (3q26) C-MYC (8q24) / SE 7 TC KBI-10704 50ON MYCN (2p24) / LAF (2q11) KBI-10706 52ON C-MET (7q31) / SE 7 KBI-10719 60ON AURKA (20q13) / 20q11 KBI-10721 61ON AURKB (17p13) / SE 17 KBI-10722 61ON TOP2A (17q21) / SE 17 KBI-10724 47Oncology Probes - Solid TumorsON PPARγ (3p25) Break KBI-10707 51ON EWSR1 (22q12) Break KBI-10708 55ON hTERT (5p15) / 5q31 (tissue) KBI-10709 59ON p16 (9p21) / 9q21 (tissue) KBI-10710 50ON MLL (11q23) / SE 11 KBI-10711 53ON SRD (1p36) / SE 1(1qh) KBI-10712 53ON SYT (18q11) Break KBI-10713 56ON CHOP (12q13) Break KBI-10714 56ON FUS (16p11) Break KBI-10715 57ON FKHR (13q14) Break KBI-10716 57ON MDM2 (12q15) / SE 12 KBI-10717 58ON CDK4 (12q13) / SE 12 KBI-10725 58ON TMPRSS2-ERG (21q22) Del, Break, TC KBI-10726 63ON IGH (14q32) Break (tissue) KBI-10729 63ON BCL6 (3q27) Break (tissue) KBI-10730 64ON MALT (18q21) Break (tissue) KBI-10731 64ON ZNF217 (20q13) / 20q11 KBI-10733 48ON CCND1 (11q13) / SE 11 KBI-10734 62ON TOP2A (17q21) / Her-2/neu (17q12) / SE 17 TC KBI-10735 48ON MDM4 (1q32) /SE 1 KBI-10736 54ON FGFR1 (8p12) Break KBI-10737 49ON p53 (17p13) / SE 17 (tissue) KBI-10738 6546ON PTEN (10q23) / SE 10 KBI-10718 60ON TFE3 (Xp11) Break KBI-10741 65

Breast CancerON ERBB2, Her2/Neu (17q12) / SE 17The Her2/Neu gene encodes a receptor tyrosine kinase involvedin growth factor signaling. Overexpression of this gene is seen inabout 20% of invasive breast cancers and is associated with poorsurvival. Her2 gene amplification is a permanent genetic changethat results in this continuous overexpression of Her2. A drugcalled trastuzumab (commonly known as Herceptin) has beendeveloped to be effective against Her2-positive breast cancer.Her2/Neu amplification is also observed in a variety of othertumors, such as prostate, lung, colon and ovary carcinoma.The Her2/Neu (17q12) specific DNA probe is optimized to detectcopy numbers of the Her2/Neu (ERBB2) gene region at region17q12. The chromosome 17 satellite enumeration probe (SE 17)at D17Z1 is included to facilitate chromosome identification.ON TOP2A (17q21) / SE 17The Topoisomerase2A enzyme, which is vital for the cellbecause of its role in cell replication and repair, catalyzesthe relaxation of supercoiled DNA molecules to create areversible double-strand DNA break. This enzyme is alsothe target of a number of cytotoxic agents, namely TOP2Ainhibitors (anthracyclines, etoposide, teniposide).The dual-color probe is optimized to detect amplifications(copy numbers) or deletions of the TOP2A gene region atthe 17q21. The chromosome 17 satellite enumeration probe(SE 17) at D17Z1 is included to facilitate chromosomeidentification.Cat.# KBI-10701 ERBB2, Her2/Neu (17q12) / SE 17Cat.# KBI-10724 TOP2A (17q21) / SE 17D17Z1RH 11280517q12D17Z1D17S123817q21ERBB2460 KBTOP2A360 KB17D17S70017D17S2011ERBB2, Her2/Neu (17q12) / SE 17 probe hybridized to breast tumortissue showing amplification of Her2/Neu (ERBB2)/ SE 17.Literature:Pauletti et al, 1996, Oncogene, 13: 63-72.Xing, et al, 1996, Breast Cancer Res Treat, 39: 203-212.Ordering information Color Tests Cat#ON ERBB2, Her2/Neu (17q12) / SE 17 red/green 10 KBI-10701ON ERBB2, Her2/Neu (17q12) / SE 17 red/green 50 KBI-14701TOP2A (17q21) / SE 17 probe hybridized to breast tissue (2R2G).Literature:Järvinen et al, 1999, Genes, Chromosomes and Cancer 26; 142-150Järvinen et al, 2000, Am. J. Pathology 156; 639-647Ordering information Color Tests Cat#ON TOP2A (17q21) / SE 17 red/green 10 KBI-10724Oncology Probes - Solid Tumors47

ON TOP2A (17q21) / Her2 (17q12) / SE 17 Triple-Color ProbeThe presence of both TOP2A amplification and deletion inadvanced cancer are associated with decreased survival,and occur frequently and concurrently with Her2 geneamplification.The TOP2A (17q21)/ Her2 (17q12)/ SE 17 probe is designedas a triple-color to detect amplification at 17q12 as wellas amplifications or deletions at 17q21. The chromosome17 satellite enumeration probe (SE 17) at D17Z1 in blue isincluded to facilitate chromosome identification.ON ZNF217 (20q13) / 20q11Zinc-finger protein 217 (ZNF217) is a Kruppel-like zinc-fingerprotein located at 20q13.2, within a region of recurrentmaximal amplification in a variety of tumor types, andespecially breast cancer cell lines and primary breast tumors.Copy number gains at 20q13 are also found in greater than25% of cancers of the ovary, colon, head and neck, brain,and pancreas, often in association with aggressive tumorbehavior. ZNF217 is considered a strong candidate oncogenethat may have profound effects on cancer progression, whichis transcribed in multiple normal tissues, and overexpressed inalmost all cell lines and tumors in which it is amplified.The ZNF217 (20q13) specific DNA probe is optimized to detectcopy numbers of 20q at 20q13. The 20q11 probe is includedto facilitate chromosome identification.Cat.# KBI-10735 TOP2A (17q21) / Her2 (17q12) / SE 17Cat.# KBI-10733 ZNF217 (20q13) / 20q11RH 112805SHGC-144070ERBB2460 KB20q11.21MAPRE1600 KBD17Z117q12RH57467D17S7001717q2120D20S48020q13ZNF217570 KBD17S1238D20S876TOP2A360 KBD17S2011Oncology Probes - Solid TumorsTOP2A (17q21)/ Her2(17q12) / SE 17 TC probe hybridized to breasttumor tissue showing amplification of TOP2A/Her2.Literature:Järvinen et al, 1999, Genes, Chromosomes and Cancer 26; 142-150Järvinen et al, 2000, Am. J. Pathology 156; 639-647Ordering information Color Tests Cat#ON TOP2A (17q21) / Her 2 / SE 17 red/green 10 KBI-10735ZNF217 (20q13) / 20q11 probe hybridized to tissue (2R2G).Literature:Tanner M et al, 2000, Clin Cancer Res, 6; 1833-1839Ginestier C et al, 2006, Clin Cancer Res, 12; 4533-4544Ordering information Color Tests Cat#ON ZNF217 (20q13) / 20q11 red/green 10 KBI-1073348

ON FGFR1 (8p12) BreakFGFR1 (fibroblast growth factor receptor 1) expression hasbeen shown to play pivotal roles in mammary developmentand breast cancer tumorigenesis. It has been shown thatFGFR1 amplification is found in up to 10% of breast cancersand is significantly more prevalent in patients > 50 years ofage and in tumors that lack HER2 expression. Even thoughthe prognostic impact of FGFR1 amplification in breast cancerstill remains unclear, the functional data demonstrating thatFGFR1 signaling is required for the survival of breast cancercells harboring FGFR1 amplification and the relatively highprevalence of FGFR1 amplification in breast cancer supportthe idea that this gene may be a useful therapeutic targetfor a subgroup of breast cancer patients with FGFR1 geneamplification.The FGFR1 (8p12) break-apart probe is optimized to detecttranslocations involving the FGFR1 gene region at 8p12 in adual-color, split assay on metaphase/interphase spreads andparaffin embedded tissue sections.Cat.# KBI-10737 FGFR1 (8p12) BreakD8S23318p12510 KBFGFR1600 KB8WI-16234FGFR1 (8p12) Break probe hybridized to patient material showinga break at 8p12 (1RG1R1G).Literature:Smedley et al, 1998, Hum Mol Genet. 7; 627-642.Sohal et al, 2001, Genes Chrom. Cancer 32; 155-163.Ordering information Color Tests Cat#ON FGFR1 (8p12) Break red/green 10 KBI-10737Oncology Probes - Solid Tumors49

Bladder CancerON p16 (9p21) / 9q21 (tissue)Homozygous and hemizygous deletions of 9p21 are theearliest and most common genetic alteration in bladdercancer. The p16 (INK4A) gene has been identified as tumorsuppressor gene in this region which is commonly deleted inbladder cancer. The loss of DNA sequences on chromosomalbands 9p21-22 has been documented also in a variety ofmalignancies including leukemias, gliomas, lung cancers, andmelanomas.The p16 (9p21) specific DNA probe is optimized to detectcopy numbers of the p16 gene region at region 9p21. The9q21 region probe is included to facilitate chromosomeidentification.Cervical CancerON CC hTERC (3q26) / C-MYC (8q24) / SE 7 TCCervical cancer, a potentially preventable disease, remainsthe second most common malignancy in women worldwide.The most consistent chromosomal gain in aneuploid tumorsof cervical squamous cell carcinoma mapped to chromosomearm 3q, including the human telomerase gene locus (hTERC)at 3q26. High-level copy number increases were also mappedto chromosome 8. Integration of HPV (Human Papilloma Virus)DNA sequences into C-MYC chromosomal regions have beenrepeatedly observed in cases of invasive genital carcinomasand in cervical cancers. The hTERC (3q26) specific DNA Probe isoptimized to detect copy numbers of the hTERC gene region atregion 3q26. The C-MYC (8q24) specific DNA probe is optimizedto detect copy numbers of the C-MYC gene region at 8q24. Thechromosome 7 satellite enumeration probe (SE 7) at D7Z1 isincluded as ploidy control.Cat.# KBI-10710 p16 (9p21) / 9q21 (tissue)Cat.# KBI-10704 Cervical Cancer hTERC (3q26)/ C-MYC (8q24) / SE 7 Triple-Color9p21D9S1749p16400 KBRH779669q21p15D9S975C-MYC570 KB9RH179193q26.2 hTERC370 KB8RH133888q24.1RH106063Oncology Probes - Solid Tumors50p16 (9p21) / 9q21 (tissue) probe hybridized to tissue (2R2G).Literature:Stadler et al, 1994, Cancer Res, 54: 2060-2063.Williamson et al, 1995, Hum Mol Genet, 4: 1569-1577.Ordering information Color Tests Cat#ON p16 (9p21) / 9q21 (tissue) red/green 10 KBI-10710CC hTERC (3q26) / C-MYC (8q24) / SE 7 TC probe hybridized to aPAP smear (destained) showing 3q26 and 8q24 amplification.The SE 7 control probe indicates a non-triploid karyotype (2B).Image kindly provided by Dr Weimer, KielLiterature:Heselmeyer et al, 1996, PNAS, 93: 479-484.Herrick et al, 2005, Cancer Res, 65: 1174-1179.Ordering information Color Tests Cat#ON CC hTERC (3q26) / C-MYC (8q24) / SE 7 TC red/green 10 KBI-10704

Thyroid CarcinomaPapillary thyroid carcinoma (PTC) is the mostfrequent primary carcinoma of the thyroid gland.The follicular carcinomas are associated withendemic goiter and a diet with low iodine intake.PTC, conversely, are multifocal and are associatedwith prior radiation and high iodine intake.ON PPARγ (3p25), BreakFollicular thyroid carcinoma is associated with thechromosomal translocation t(2;3)(q13;p25), fusing PAX8(2q13) with the nuclear receptor, peroxisome proliferatoractivatedreceptor γ (PPARγ). The close surrounding of PPAR isa breakpoint hot spot region, leading to recurrent alterationsof this gene in thyroid tumors of follicular origin includingcarcinomas as well as adenomas with or without involvementof PAX8.A break or split probe for PPARγ is best used to analyzetranslocation of the PPARγ (3p25) gene on formalin fixedparaffin embedded tissue for routine clinical diagnosis.Cat.# KBI-10707 PPARγ (3p25) Break3p25D351351325 KBPPARg350 KBD354563PPARγ (3p25) Break probe hybridized to patient material showinga translocation at 3p25 (1RG1R1G).Image kindly provided by Dr Valent, ParisLiterature:French et al, 2003, Am J Pathol, 162; 1053-1060.Drieschner et l, 2006, Thyroid, 16; 1091-1096.Ordering information Color Tests Cat#ON PPARγ (3p25), Break red/green 10 KBI-10707Oncology Probes - Solid Tumors51

NeuroblastomaAccording to the International Neuroblastoma RiskGrouping (INRG) Biology Committee MYCN remainsthe only genomic factor to be used currently fortreatment stratification. Common data elements tobe obtained by all groups include tumor cell ploidyand copy number/LOH status at chromosome bands1p36, 11q23, and 17q23-25.Literature:Ambros et al, 2006, Advances in Neuroblastoma ResearchON MYCN (2p24) / LAF (2q11)Amplification of the human N-myc protooncogene, MYCN, isfrequently seen either in extrachromosomal double minutesor in homogeneously staining regions of aggressivelygrowing neuroblastomas. MYCN amplification has beendefined by the INRG as > 4-fold MYCN signals comparedto 2q reference probe signals.The MYCN (2p24) specific DNA probe is optimized todetect copy numbers of the MYCN gene region at 2p24.The LAF gene region probe at 2q11 is included to facilitatechromosome identification.Cat.# KBI-10706 MYCN (2p24) / LAF (2q11)D2S26762p24.3MYCN450 KBRH1129072q11.2LAF4375 KB2Oncology Probes - Solid TumorsMYCN (2p24) / LAF (2q11) hybridized to a cell line showingamplification of MYCN on chromosome 13 and 15.Image kindly provided by Pasteur Workshop 2008, ParisLiterature:Shapiro et al, 1993, Am J Pathol, 142: 1339-1346.Corvi et al, 1994, PNAS, 91: 5523-5527..Ordering information Color Tests Cat#ON MYCN (2p24) / LAF (2q11) red/green 10 KBI-1070652

ON SRD 1p36 / SE 1(1qh)Neuroblastomas frequently have deletions of chromosome1p and amplification of the N-myc oncogene. These deletionstend to be large and extend to the telomere, but a commonregion within sub-band 1p36.3 is consistently lost. Inactivationof a tumor suppressor gene within 1p36.3 is believed to beassociated with an increased risk for disease relapse. The1p36 specific DNA probe has recently been changed to coverthe recently described smallest region of consistent deletion(SRD) between D1S2795 and D1S253.The SRD (1p36) specific DNA probe is optimized to detectcopy numbers of the 1p36 region on chromosome 1. Thechromosome 1 satellite enumeration probe (SE 1) at 1qh isincluded to facilitate chromosome identification.ON MLL (11q23) / SE 11Deletions of the long arm of chromosome 11 (11q) havebeen noted in primary neuroblastomas. It is assumedthat a tumor suppressor gene mapping within 11q23.3 iscommonly inactivated during the malignant evolution ofa large subset of neuroblastomas, especially those withunamplified MYCN.The MLL (11q23) specific DNA probe is optimized to detectamplification or deletion involving the MLL gene region at11q23 in a dual-color assay on metaphase/interphase spreads,blood smears and bone marrow cells. The Chromosome 11Satellite Enumeration probe (SE 11) at D11Z1 is included tofacilitate chromosome identification.Cat.# KBI-10712 SRD (1p36) / SE 1(1qh)Cat.# KBI-10711 MLL (11q23) / SE 111p36.3D11S976D1S2795D11Z1220 KBMLL (88KB)SHGC-14929911q23290 KB1qhCHD5530 KB11D11S4538D1S286ED1S2531SRD (1p36) / SE 1 probe hybridized to a normal metaphase (2R2G).Literature:Caron et al, 1993, Nat Genet, 4: 187-190.Cheng et al, 1995, Oncogene, 10: 291-297.White et al, 2005, Oncogene, 24: 2684-2694Ordering information Color Tests Cat#ON SRD (1p36) / SE1(1qh) red/green 10 KBI-10712MLL (11q23) / SE 11 hybridized to normal interphases (2R2G).Literature:Guo et al, 1999, Oncogene, 18: 4948-4957.Maris et al, 2001, Med Pediatr Oncol, 36: 24-27.Ordering information Color Tests Cat#ON MLL (11q23) / SE11 red/green 10 KBI-10711Oncology Probes - Solid Tumors53

ON p53 (17p13) / MPO (17q22) “ISO 17q”Gain of genetic material from chromosome arm 17q (gainof segment 17q21-qter) is the most frequent cytogeneticabnormality of neuroblastoma cells. In multivariate analysis,17q gain was more strongly associated with adverseoutcome than was either stage (Stage 4 vs other combined)or 1p status.ON MDM4 (1q32) / SE1MDM4 (also known as MDMX, murine double minute gene)is a relative of MDM2 that was identified on the basis of itsability to physically interact with p53. MDM4, like MDM2,acts as a key negative regulator of p53 by interfering withits transcriptional activity. MDM4 amplification and/oroverexpression occurs in several diverse tumors. Studiesshowed an increased MDM4 copy number in 65% of humanretinoblastomas compared to other tumors, qualifyingMDM4 as a specific chemotherapeutic target for treatmentof this tumor.The MDM4 (1q32) specific DNA probe is designed as a dualcolorassay to detect amplification at 1q32. The chromosome1 Satellite Enumeration (SE 1) probe at 1qh is included tofacilitate chromosome identification.Cat.# KBI-10011 p53 (17p13) / MPO (17q23) “ISO 17q”Cat.# KBI-10736 MDM4 (1q32) / SE 11qhRH2406MDM4440 KB1q32D1S504See probe description under CML on page 15.1Oncology Probes - Solid TumorsLiterature:Bown et al, 1999, N Engl J Med, 340: 1954-1961.O’Neill, 2001, Genes Chrom Cancer, 30: 87-90.Ordering information Color Tests Cat#ON p53 (17p13) / MPO (17q22) “ISO 17q” red/green 10 KBI-10011MDM4 (1q32) / SE 1 probe hybridized to paraffin embeddedtissue (2R2G).Literature:Riemenschneider et al, 1999, Cancer Res. 59 ; 6091-6096Danovi et al, 2004, Mol.Cell.Bio. 24; 5835-5843Ordering information Color Tests Cat#ON MDM4 (1q32) / SE 1 red/green 10 KBI-1073654

SarcomaSarcoma is a general class of less common cancersin which the cancer cells arise from or resemblenormal cells in the body known as “connectivetissues” (fat, muscle, blood vessels, deep skintissues, nerves, bones, and cartilage). The benignand malignant forms have related karyotypicchanges which provide an important resource foridentifying the additional genetic changes thatoccur in the malignant compared with the benignform. In fact, the molecular biology of soft-tissuesarcomas has provided the perfect example ofhow cytogenetic and molecular approaches cancontribute toward a clearer understanding of thedevelopment of soft-tissue sarcomas.ON EWSR1 (22q12) BreakThe translocation t(11;22)(q24;q12) has been independentlydescribed by several groups in the malignant cells of patientswith Ewing sarcoma and can be detected in more than 90%of these tumors. The translocation involves the fusion ofthe human FLI1 gene on chromosome 11, with the codingsequence of the EWS gene on chromosome 22. In about 5%of the cases, however, the EWS gene is involved in varianttranslocations. These translocations, t(21;22)(q12;q12) andt(7;22)(p22;q12) result in the fusion of EWS with ERG andETV1, respectively.The Poseidon break or split probe for EWS is optimizedto identify translocation involving the EWS gene onformalin fixed paraffin embedded tissue for routine clinicaldiagnosis.Cat.# KBI-10708 EWS (22q12) BreakRH 120772760 KB22q12EWS221200 KBD22S1023EWS (22q12) Break probe hybridized to patient materialshowing a translocation involving the EWRS1 gene region at22q12 (1RG1R1G).Literature:Zucman-Rossi, et al, 1998, PNAS, 95; 11786-11791.Bernstein et al, 2006, Oncologist, 11; 503-519.Ordering information Color Tests Cat#ON EWSR1 (22q12) Break red/green 10 KBI-10708Oncology Probes - Solid Tumors55

ON SYT (18q11) BreakThe characteristic chromosomal abnormality in synovialsarcoma is t(X;18)(p11.2;q11.2) present in 90% of patients.This translocation results in the fusion of the chromosome18 SYT gene to either of two distinct genes, SSX1 or SSX2,located on the X chromosome.A break or split probe for SYT is best used to analyzetranslocation of the SYT (SS18) gene on formalin fixed paraffinembedded tissue for routine clinical diagnosis.ON CHOP (12q13) BreakLiposarcoma is one of the most frequent sarcomas in adults,representing 10 to 16 percent of soft tissue sarcomas.Most patients with round cell/myxoid liposarcoma havean acquired t(12;16)(CHOP-FUS) or t(12;22)(CHOP-EWS)translocation, both of which involve the CHOP gene at12q13. A break or split probe for CHOP is best used to analyzetranslocation of the CHOP (12q13) gene on formalin fixedparaffin embedded tissue for routine clinical diagnosis.The CHOP (12q13) Break probe is optimized to detecttranslocations involving the CHOP gene region at 12q13 ina dual-color, split assay.Cat.# KBI-10713 SYT (18q11) BreakCat.# KBI-10714 CHOP (12q13) BreakRH 22533RH 7535318q111077 KB12q13700 KBSYT (SS18)CHOP18RH 118756717 KB12RH 118682680 KBOncology Probes - Solid TumorsSYT (18q11) Break probe hybridized to patient materialshowing translocation of the SYT (SS18) gene region at18q11 (1RG1R1G).Literature:Kawai et al, 1998, NEJM, 338; 153-160Surace et al, 2004, LabInvest., 84; 1185-1192Ordering information Color Tests Cat#ON SYT (18q11) Break red/green 10 KBI-10713CHOP (12q13) Break probe hybridized to a normalmetaphase (2RG).Literature:Panagopoulos et a, 1994, Cancer Res, 54; 6500-6503.Schoenmakers et al, 1994, Genomics, 20; 210-222.Ordering information Color Tests Cat#ON CHOP (12q13) Break red/green 10 KBI-1071456

ON FUS (16p11) BreakThe FUS gene was originally shown to be rearranged in myxoidliposarcomas harboring a t(12;16)(q13;p11) translocation.FUS has been shown to be involved also in otherrecombinations: with ERG in acute myeloid leukemia carryinga t(16;21), with ATF1 in band 12q13 in angiomatoid fibroushistiocytoma, and with CREB3L2 in fibromyxoid sarcoma.A break or split probe for FUS is best used to analyzetranslocation of the FUS (16p11) gene on formalin fixedparaffin embedded tissue for routine clinical diagnosis.ON FKHR (13q14) BreakThe t(2;13) is associated with alveolar rhabdomyosarcomas.This translocation results in the formation of a chimerictranscript consisting of the 5’ portion of PAX3, includingan intact DNA-binding domain fused to the FKHR gene onchromosome 13. The t(1;13)(p36;q14) also seen in alveolarrhabdomyosarcomas results in the fusion of anothermember of the PAX family, PAX7 to the FKHR gene onchromosome 13.A break or split probe for FKHR is best used to analyzetranslocation of the FKHR (13q14) gene on formalin fixedparaffin embedded tissue for routine clinical diagnosis.Cat.# KBI-10715 FUS (16p11)Cat.# KBI-10716 FKHR (13q14) BreakD16S2574ERH 4517816p11780 KB840 KBFUS13q14FKHR(FOXO1A)16D16S2933E550 KB13D13S647690 KBFUS (16p11) Break probe hybridized to liposarcomamaterial (2RG).Literature:Shing et al, 2003, Cancer Res, 63: 4568-4576.Storlazzi et al, 2003, Hum. Mol. Genet., 12: 2349-2358.Ordering information Color Tests Cat#ON FUS (16p11), Break red/green 10 KBI-10715FKHR (13q14) Break probe hybridized to a normalmetaphase (2RG).Literature:Barr et al, 1996, Hum. Mol. Genet., 5; 15-21.Coignet et al, 1999, Genes Chrom. Cancer, 25; 222-229.Ordering information Color Tests Cat#ON FKHR (13q14) Break red/green 10 KBI-10716Oncology Probes - Solid Tumors57

ON MDM2 (12q15) / SE 12Fibrosarcoma is a rare soft-tissue tumor composed offascicles of spindled fibroblast-like cells. Gains and high-levelamplifications of 12q14–22 were the most common genomicimbalances, and reflected MDM2 amplification, therebyindicating the importance of this gene in the evolution offibrosarcomas.The MDM2 (12q15) specific DNA probe is optimized to detectcopy numbers of the MDM2 gene region at region 12q15.The Chromosome 12 Satellite Enumeration probe (SE 12) atD12Z3 is included to facilitate chromosome identification.ON CDK4 (12q13) / SE 12Amplification of the CDK4 gene region at 12q13-q15 has beenobserved in several types of cancer, especially in gliomas andsarcomas. CDK4 codes for a cyclin dependent kinase whichis involved in controlling progression through the G1 phaseof the cell cycle. The oncogenic potential of CDK4 activationhas been related to the deregulation of the G1 phase byincreasing the hyperphosphorylation of retinoblastoma tumorsuppressor protein helping to cancel its growth-inhibitoryeffects.The CDK4 (12q13) specific DNA probe is optimized to detectcopy numbers of the CDK4 gene region at 12q13. Thechromosome 12 satellite enumeration probe (SE 12) at D12Z3is included to facilitate chromosome identification.Cat.# KBI-10717 MDM2 (12q15) / SE 12Cat.# KBI-10725 CDK4 (12q13) / SE 12D12Z3D12S1382ED12Z3D12S1266MDM212q15528 KB12q13CDK4900 KBD12S1497D12S15291212Oncology Probes - Solid Tumors58MDM2 (12q15) / SE 12 hybridized to a normalmetaphase (2R2G).Literature:Mitchell et al, 1995, Chrom. Res., 3; 261-262.Reifenberger et al, 1996, Cancer Res., 15; 5141-5145.Ordering information Color Tests Cat#ON MDM2 (12q15) / SE12 red/green 10 KBI-10717CDK4 (12q13) / SE 12 probe hybridized to liposarcoma tissueshowing multiple amplification involving the CDK4 gene region at12q13 (3+R2G).Image kindly provided by Dr. Sapi, Hungary.Literature:Kuhnen et al, 2002, Virchows Arch 441 ; 299-302Shimada et al, 2006, Hum Path 37(9) ; 1123-1129Ordering information Color Tests Cat#ON CDK4 (12q13) / SE 12 red/green 10 KBI-10725

Different Cancer typesON EGFR, Her-1 (7p11) / SE 7Epidermal growth factor receptor (EGFR) is a cell membraneprotein, providing signal transduction and cell growth. It is amember of the Her or Erb-B family of type I receptor tyrosinekinases and implicated in the development and progressionof cancer of the lung, breast, intestine, and other organs.EGFR was found to act as a strong prognostic indicator inhead and neck, ovarian, cervical, bladder and oesophagealcancers. In these cancers, increased EGFR expression wasassociated with reduced recurrence-free or overall survival.The EGFR (7p11) specific DNA probe is optimized to detectcopy numbers of the EGFR (Her1) gene region at region 7p11.The chromosome 7 satellite enumeration probe (SE 7) at D7Z1is included to facilitate chromosome identification.ON hTERT (5p15) / 5q31 (tissue)Amplification of the hTERT gene at band 5p15 has beenobserved in a variety of cancer, particularly lung cancer,cervical tumors, and breast carcinomas. Several studies haverevealed a high frequency of hTERT gene amplification inhuman tumors, which indicates that the hTERT gene maybe a target for amplification during the transformation ofhuman malignancies and that this genetic event probablycontributes to a dysregulation of hTERT/telomerase occurringin a subset of human tumors.The hTERT (5p15) probe is designed as a dual-color assay todetect amplification at 5p15. The CDC25C/EGR1 (5q31) generegion probe is included as internal control.Cat.# KBI-10702 EGFR, Her1 (7p11) / SE 7Cat.# KBI-10709 hTERT (5p15) / 5q31 (tissue)5p15.3D7Z1RH1058587p11.2HER1-EGFR340 KBD5S1981hTERTD5S2269190 KBD7S2357RH480325q31.2CDC25C7645 KB5EGR1D5S597EGFR, Her1 (7p11) / SE 7 hybridized to colon tissue (2R2G).Literature:Wang et al, 1993, Jpn J Hum Genet, 38: 399-406.Nicholoson et al, 2001, Eur J Cancer, 37: 9-15.Ordering information Color Tests Cat#ON EGFR, Her-1 (7p11) / SE 7 red/green 10 KBI-10702hTERT (5p15) / 5q31 (tissue) probe hybridized to paraffineembedded tissue (2R2G).Literature:Bryce et al, 2000, Neoplasia, 2; 197-201.Zhang et al, 2000, Cancer Res, 60; 6230-6235.Ordering information Color Tests Cat#ON hTERT (5p15) / 5q31 (tissue) red/green 10 KBI-10709Oncology Probes - Solid Tumors59

ON PTEN (10q23) / SE 10The gene ‘phosphatase and tensin homolog deleted onchromosome 10’ (PTEN), is a tumor suppressor locatedat chromosome 10q23, that plays an essential role in themaintenance of chromosomal stability, cell survival andproliferation. Loss of PTEN has been found in a wide numberof tumors, and his important role is demonstrated by the factthat it is the second most frequently mutated gene after p53.Loss of PTEN significantly correlates with the advanced formsof gliomas, but also of prostate cancer and breast tumors.The PTEN (10q23) specific DNA probe is optimized to detectcopy numbers of the PTEN gene region at region 10q23.The Chromosome 10 Satellite enumeration probe (SE 10) atD10Z1 is included to facilitate chromosome identification.ON C-MET (7q31) / SE 7The C-MET proto-oncogene is a receptor-like tyrosine kinasethat drives a physiological cellular program important fordevelopment, cell movement, cell repair, cellular growth.Aberrant execution of the program has been associated toneoplastic transformation, invasion and metastasis. Activationof C-MET has been reported in a significant percentage ofhuman cancers and is amplified during the transition betweenprimary tumors and metastasis.The C-MET (7q31) specific DNA probe is optimized to detectcopy numbers of the C-MET gene region at region 7q31. TheChromosome 7 Satellite enumeration probe (SE 7) at D7Z1 isincluded to facilitate chromosome identification.Cat.# KBI-10718 PTEN (10q23) / SE 10Cat.# KBI-10719 C-MET (7q31) / SE 7D10Z1RH113215PTEN480 KBD7Z1D7S3086WI-2224910q23C-MET420 KBSHGC-1431537q31RH110508107Oncology Probes - Solid TumorsPTEN (10q23) / SE 10 probe hybridized to prostate cancer materialshowing deletion of PTEN gene region at 10q23 (1R2G).Image kindly provided by Portuguese Cancer Inst., PortoLiterature:Cairns et al, 1997, Cancer Res, 57 ; 4997-5000Hermans et al, 2004, Genes Chrom Cancer, 39; 171-184Ordering information Color Tests Cat#ON PTEN (10q23) / SE 10 red/green 10 KBI-10718C-MET (7q31) / SE 7 probe hybridized to colon tissue (2R2G).Literature:Hara et al, 1998, Lab Invest 78; 1143-1153.Tsugawa et al., 1998, Oncology 55; 475-481.Ordering information Color Tests Cat#ON C-MET (7q31) / SE 7 red/green 10 KBI-1071960

ON AURKA (20q13) / 20q11Aurora kinase A (AURKA) covers the fundamental role ofregulating proper centrosome function, important to maintaingenomic stability during cell division and to ensure equalsegregation of replicated chromosomes to daughter cells.Deregulated duplication and distribution of centrosomes hasbeen implicated in mechanisms leading to mitotic spindleaberrations, aneuploidy, and genomic instability that are seenin many different tumor types. Consistent with this, AURKAamplification has been detected in approximately 12% ofprimary breast tumors, as well as in breast, ovarian, colon,prostate, neuroblastoma and cervical cancer cell lines. Recentinvestigations on new drugs developments have focused onthe importance of aurora kinases for tumor suppression.ON AURKB (17p13) / SE 17Aurora kinase B (AURKB) localizes to microtubules, and isa key regulator of the mitotic cell division and chromosomesegregation processes. Gain of function of AURKB correlateswith cell proliferation, induction of multinuclear cells, andchromosomal instability. The significant interest of the genein cancer diagnostics is related to the driving function ofAURKB in tumor progression, histological differentiation,and metastasis. AURKB is predictive for the aggressiverecurrence of many different types of tumors, includinghepatocellular carcinoma and oral squamous cell carcinoma.Recently new drugs have been under investigation for theircapacity of interfering with the aurora kinases activityrelated to tumor-suppressor effects.The AURKA (20q13) specific DNA probe is optimized todetect copy numbers of the AURKA gene region at region20q13. The 20q11 specific DNA probe is included to facilitatechromosome identification.The AURKB (17p13) specific DNA probe is optimized to detectcopy numbers of the AURKB gene region at region 17p13.The Chromosome 17 Satellite Enumeration (SE 17) probe atD17Z1 is included to facilitate chromosome identification.Cat.# KBI-10721 AURKA (20q13) / 20q11Cat.# KBI-10722 AURKB (17p13) / SE 17SHGC-144070D17S561MAPRE120q11.21600 KBD17Z117p13AURKB510 KBRH574672020q13SHGC 12066AURKA500 KB17D17S647RH75698AURKA (20q13) / 20q11 probe hybridized to breast tumortissue (2R2G).Literature:Sen et al, 2002, J of Nat Canc Inst 94; 1320-1329.Lassmann et al, 2007, Clin Cancer Res 13; 4083-4091Ordering information Color Tests Cat#ON AURKA (20q13) / 20q11 red/green 10 KBI-10721AURKB (17p13) / SE 17 probe hybridized to tumortissue (2R2G).Literature:Smith et al, 2005, Br J Cancer, 93; 719-729Ordering information Color Tests Cat#ON AURKB (17p13) / SE 17 red/green 10 KBI-10722Oncology Probes - Solid Tumors61

ON CCND1 (11q13) / SE 11CCND1 (also named Cyclin D1 or BCL1) is a key cell cycleregulator of the G1 to S phase progression. The bindingof cyclin D1 to cyclin-dependent kinase (CDKs) leads tothe phosphorylation of retinoblastoma protein (pRb),subsequently triggering the release of E2F transcriptionfactors to allow G1 to S phase progression of the cell cycle.Consistent with this function, overexpression of cyclin D1results in a more rapid progression from the G1 to S phasetransition and in a reduced serum dependency in fibroblastcells, characteristics typically seen in cancer cells.Amplification of cyclin D1 plays pivotal roles in thedevelopment of a subset of human cancers includingparathyroid adenoma, breast cancer, colon cancer, lymphoma,melanoma, and prostate cancer.The CCND1 (11q13) specific DNA Probe is optimized todetect copy numbers of the CCND1 gene region at region11q13. The Chromosome 11 Satellite Enumeration (SE11) probe at D11Z1 is included to facilitate chromosomeidentification.Cat.# KBI-10734 CCND1 (11q13) / SE 11D11Z1RH10354711q13CCND1450 KBD11S292711Oncology Probes - Solid TumorsCCDN1 (11q13) / SE 11 probe hybridized to patient interphases/metaphase showing CCDN1 (11q13) amplification with polyploidyfor chromosome 11.Literature:Okami et al, 1999, Oncogene 18; 3541-3545.Freier et al, 2003, Cancer Res; 1179-1182Ordering information Color Tests Cat#ON CCND1 (11q13) / SE 11 red/green 10 KBI-1073462

TMPRSS2-ERG (21q22) Del, Break, TCThe transmembrane protease serine 2 gene (TMPRSS2) isinvolved in gene fusions with ERG, ETV1 or ETV4 in prostatecancer. In recent studies it has been described that theexpression of the TMPRSS2-ERG fusion gene is a strongprognostic factor for the risk of prostate cancer recurrencein prostate cancer patients treated by surgery.The TMPRSS2-ERG rearrangement probe is optimized todetect the deletion between TMPRSS2 and ERG at 21q22associated with the TMPRSS2-ERG fusion in a triple-colordeletion assay. It also detects translocations involving theTMPRSS2 region such as ETV1 t(7;21), or ETV4 t(17;21).ON IGH (14q32) Break (tissue)Chromosomal rearrangements involving the immunoglobulinheavy chain gene (IGH) at 14q32 are observed in 50% ofpatients with B-cell non-Hodgkin’s lymphoma (NHL) andmany other types of Lymphomas. More than 50 translocationpartners with IGH have been described. In particular t(8;14),is associated with Burkitt’s lymphoma, t(11;14) is associatedwith Mantle cell lymphoma, t(14;18) is observed in a highproportion of follicular lymphomas and t(3;14) is associatedwith Diffuse Large B-Cell Lymphoma.The IGH (14q32) break probe is optimized to detecttranslocations involving the IGH gene region at 14q32 ina dual-color, split assay. Kreatech has developed this probefor the specific use on cell material (KBI-10601), or for theuse on tissue (KBI-10729).Cat.# KBI-10726 TMPRSS2-ERG (21q22) Del, Break, TCCat.# KBI-10729 ON IGH (14q32) Break (tissue)D21S143921RH123924ERGETS2D21S34921q22TMPRSS2700 KBGAP 2.3 MB600 KB14D14S683EJAG2IGHCIGHJIGHD14q32IGHV600 KB400 KBD14S308700 KBD21S1820TMPRSS2-ERG (21q22) rearrangement probe hybridized to prostatecarcinoma tissue showing a deletion of the TMPRSS2 (21q22) generegion associated with TMPRSS2-ERG fusion (1RGB 1RB).Image kindly provided by Dr. Texeira, Porto.Literature:Perner et al, 2006 Cancer Res 66; 8337-8341Hermans et al, 2006, Cancer Res 66; 10658-10663Attard et al, 2008, Oncogene 27; 253-263Ordering information Color Tests Cat#TMPRSS2-ERG (21q22) Del, Break, TC red/green 10 KBI-10726IGH (14q32) Break probe hybridized to patient material showinga partial deletion of 14q32 (1RG1R).Literature:Taniwaki et al, 1994, Blood, 83: 2962-1969.Gozetti et al, 2002, Cancer Research, 62: 5523-5527.Ordering information Color Tests Cat#ON IGH (14q32) Break (tissue) red/green 10 KBI-10729Oncology Probes - Solid Tumors63

ON BCL6 (3q27) Break (tissue)Chromosomal translocations involving band 3q27 withvarious different partner chromosomes represent a recurrentcytogenetic abnormality in B-cell non-Hodgkin’s lymphoma.A FISH strategy using two differently labeled flanking BCL6probes provides a robust, sensitive, and reproducible methodfor the detection of common and uncommon abnormalities ofBCL6 gene in interphase nuclei. Kreatech has developed thisprobe for the specific use on cell material (KBI-10607), or forthe use on tissue (KBI-10730).ON MALT (18q21) Break (tissue)Low grade malignant lymphomas arising from mucosaassociated lymphoid tissue (MALT) represent a distinctclinicopathological entity. The three major translocationsseen in MALT lymphomas are t(11;18)(q21;q21)/API2-MALT1, t(14;18)(q32;q21)/IGH-MALT1 and t(1;14)(p22;q32)/IGH-BCL10. A break or split probe for MALT (18q21) isbest used to analyze translocation of the MALT gene onformalin fixed paraffin embedded tissue for routine clinicaldiagnosis.Note: Two different breakpoint regions have been identified,the major breakpoint region (MBR) is located within the5’ noncoding region of the BCL6 proto-oncogene, while theatypical breakpoint region (ABR) is located approximately 250kb proximal to the BCL6 gene. The Poseidon BCL6 (3q27) isdesigned in a way to flank both possible breakpoints, therebyproviding clear split signals in either case.Kreatech has developed this probe for the specific use oncell material (KBI-10608), or for the use on tissue (KBI-10731).Cat.# KBI-10730 ON BCL6 (3q27) Break (tissue)Cat.# KBI-10731 ON MALT (18q21) Break (tissue)D18S1055D3S4060345 KB550 KBMALT18q21ABR*BCL6MBR*350 KB18680 KBD3S3245RH 1038853q273ABR* atypical breakpoint regionMBR* major breakpoint regionOncology Probes - Solid TumorsBCL6 (3q27) Break probe hybridized to patient material showingboth normal (2RG) and aberrant signals (1RG1R1G).Image kindly provided by Prof Siebert, KielLiterature:Butler et al, 2002, Cancer Res, 62; 4089-4094.Sanchez-Izquierdo, 2001, Leukemia, 15; 1475-1484.Ordering information Color Tests Cat#ON BCL6 (3q27) Break (tissue) red/green 10 KBI-10730MALT (18q21) Break tissue probe hybridized to paraffinembedded material (2RG).Literature:Morgan et al, 1999, Cancer Res, 59; 6205-6213Dierlamm et al, 2000, Blood, 96; 2215-2218.Ordering information Color Tests Cat#ON MALT (18q21) Break (tissue) red/green 10 KBI-1073164

ON p53 (17p13) / SE 17 (tissue)The p53 tumor suppressor gene at 17p13, has beenshown to be implicated in the control of normal cellularproliferation, differentiation, and apoptosis. Allelic loss,usually by deletion, and inactivation of p53 have beenreported in numerous tumor types and are associated withpoor prognosis in CLL.The p53 (17p13) specific DNA probe is optimized todetect copy numbers of the p53 gene region at 17p13. Thechromosome 17 satellite enumeration probe (SE 17) atD17Z1 is included to facilitate chromosome identification.ON TFE3 (Xp11) BreakAbnormalities of Xp11.2 region have often been observed inpapillary renal cell carcinomas and are sometimes the solecytogenetic abnormality present. The transcription factorbinding to IGHM enhancer 3 (TFE3) gene, which encodesa member of the helix-loop-helix family of transcriptionfactors, is located in this critical region and can be fusedto various other chromosomal regions by translocation.Known fusion partners are NONO (Xq12), PRCC (1q21),SFPQ (1p34), CLTC (17q23) and ASPSCR1 (17q25).The TFE3 (Xp11) Break probe is optimized to detecttranslocations involving the TFE3 gene region at Xp11.2 ina dual-color, split assay.Cat.# KBI-10738 p53 (17p13) / SE 17 (tissue)Cat.# KBI-10741 TFE3 (Xp11) BreakDXS6784D17Z117p13D17S960Xp11.2525 KBTFE3330 KBP53425 KB17D17S634DXS1522XP53 (17p13) / SE 17 (tissue) probe hybridized to paraffinembedded tissue (2R2G).Literature:Amiel A et al, 1997, Cancer Gener.Cytogenet,, 97; 97-100Drach J et al, 1998, Blood, 92; 802-809Ordering information Color Tests Cat#ON p53 (17p13) / SE 17 (tissue) red/green 10 KBI-10738TFE3 (Xp11) Break probe hybridized to renal cell carcinomashowing a translocation at Xp11 (1RG1R1G).Image kindly provided by Dr. Desangles, ParisLiterature:Sidhar et al, 1996, Hum Mol Genet, 5; 1333-1338.Weterman et al., 1996, Proc Natl, Acad Sci, 93; 15294-15298.Ordering information Color Tests Cat#ON TFE3 (Xp11) Break red/green 10 KBI-10741Oncology Probes - Solid Tumors65

Preimplantation Genetic ScreeningFISH is the current gold standard to determine the chromosomal constitution of an embryo. In contrast tokaryotyping it can be used on interphase chromosomes, so that it can be applied on polar bodies, blastomeres andother single cell samples. FISH is therefore accepted as a routine method in preimplantation genetic screening(PGS) in determining chromosome aneuploidies prior to implanting an embyro and increases the success rate ofan IVF-mediated pregnancy.Preimplantation Genetic ScreeningMultiStar 24 FISHMultiStar 24 FISH consists of four DNA probe mixes eachhybridizing to six different chromosomes using six differentfluorochromes. It can be applied in lymphocytes, sperm andblastomeres. The fully optimized protocol consists of three15-30 minutes hybridizations followed by an overnight one. Inbetween the individual hybridizations, the preceding probesare washed off after imaging the results. The morphologyof the cell types is retained despite repeated denaturation,hybridization and post hybridization washes. Moreover theentire protocol can be completed within 24 hours, which fitsthe window for clinical PGS application. This novel methodeliminates the bottleneck perceived when using FISH byomitting key chromosomes relevant to implantation failurenot covered in a limited panel.Setup of the different layersAll DNA probes are labeled with PlatinumBright based on theUniversal Linkage System (ULS), KREATECH´s proprietary nonenzymaticlabeling technology capable of linking fluorescentlabels or haptens to any nucleic acid of interest.ColorMetaphase preparation from male lymphocyte cellsvisualizing all 24 chromosomes.Image kindly provided by Prof. D. Griffin, University of Kent, United KingdomThe probes required to provide information for 24 chromosomescomprise four panels each containing 6 chromosome-specificidentifier sequences each labelled with a different fluorochrome.The first 3 panels use centromeric sequences (Panel 1: chromosomes1,3,4,6,7,8; Panel 2: chromosomes 9,10,11,12,17,20 and Panel3: chromosomes 2,15,16,18,X,Y) . In contrast, Panel 4 used forthe final round of hybridization uses unique sequence probes forchromosomes 5,13,14,19,21,22 since centromeric sequenceswere not available for these chromosomes. A combination ofseparate probe denaturation for 10 minutes followed by a shortco-denaturation between probe and sample is used. Panels 1-3require short hybridization times (15 minutes) whereas Panel 4requires overnight hybridization.Label PlatinumBright 405 PlatinumBright 415 PlatinumBright 495 PlatinumBright 547 PlatinumBright 590 PlatinumBright 647MultiStar Panel 1 7 1 6 8 3 4MultiStar Panel 2 11 9 20 12 10 17MultiStar Panel 3 18 Y X 16 2 1566MultiStar Panel 4 19 5 21 22 13 14

PreimpScreen PolB (13,16,18,21,22)PreimpScreen PolB is designed for determining chromosomecopy number in polar bodies.PreimpScreen Blas (13,18,21,X,Y)PreimpScreen Blas is designed for determination of chromosomecopy number in blastomeres.The first polar body is removed from the unfertilized oocyte,and the second polar body from the zygote, shortly afterfertilization. The main advantage of the use of polar bodiesin preimplantation genetic screening (PGS) is that theyare not necessary for successful fertilization or normalembryonic development, thus ensuring no deleterious effectfor the embryo. In some countries, where the legislationbans the selection of preimplantation embryos, polar bodyanalysis is the only possible method to perform PGS. Thebiopsy and analysis of the first and second polar bodies canbe completed before syngamy, which is the moment fromwhich the zygote is considered an embryo and becomesprotected by the law.Cleavage-stage biopsy is generally performed the morningof day three post-fertilization, when normally developingembryos reach the eight-cell stage. The biopsy is usuallyperformed on embryos with less than 50% of anucleatedfragments and at an 8-cell or later stage of development.The main advantage of cleavage-stage biopsy over polarbody (PB) analysis is that the genetic input of both parentscan be studied, and therefore currently is the prevalentmethod when doing in situ hybridizations in preimplantationgenetic screening.Pseudo color image using PreimpScreen PolB (KBI-40050) on ametaphase spread from lymphocytes showing two signals each ofchromosomes 13, 16, 18, 21, and 22, respectively.Ordering informationPseudo-color image on a healthy female blastomer usingPreimpScreen Blas (13,18,21,X,Y) FISH panel, KBI-40051.Image kindly provided by Prof. D. Griffin, University of Kent, United KingdomProduct Description Tests Cat#PreimpScreen PolB (13,16,18,21,22) Five-color FISH-mix consisting of DNA probes specific for chromosomes 13, 16, 18, 21, and 22 20 KBI-40050PreimpScreen Blas (13,18,21,X,Y) Five-color FISH-mix consisting of DNA probes specific for chromosomes 13, 18, 21, X, and Y 20 KBI-40051MultiStar 24 FISHFISH probe panel for visualizing all 24 chromosomes (including the four panels KBI-40061,KBI-40062, KBI-40063, and KBI-40064)10 KBI-40060MultiStar FISH Panel 1 FISH panel of centromeric probes for chromosomes 1, 3, 4, 6, 7, and 8 10 KBI-40061MultiStar FISH Panel 2 FISH panel of centromeric probes for chromosomes 9, 10, 11, 12, 17, and 20 10 KBI-40062MultiStar FISH Panel 3 FISH panel of centromeric probes for chromosomes 2, 15, 16, 18, X, and Y 10 KBI-40063MultiStar FISH Panel 4 FISH panel of unique sequence probes for chromosomes 5, 13, 14, 19, 21, and 22 10 KBI-40064Preimplantation Genetic Screening67

Prenatal probesPrenatal cytogenetic analysis requires the isolation of metaphase chromosomes and takes 7-14 days for thefinal results. This waiting period tends to cause psychological distress for pregnant women and their families.Aneuploidies of 5 chromosomes (13, 18, 21, X, Y) account for 95% of the chromosomal aberrations that causeinfants born with defects. Fluorescent labeled DNA probes of the 13, 18, 21, X, Y chromosomes can be usedon uncultured cells obtained directly from amniotic fluid. The FISH rapid technique allows to reliably detectnumerical aberrations for these chromosomes.While not all chromosome abnormalities can be identified simply by counting specific chromosomes within acell, the majority of the most common abnormalities of chromosome number, including Down syndrome (trisomy21), trisomy 18, trisomy 13, Klinefelter syndrome (47,XXY), triple-X syndrome (47,XXX), Turner syndrome (45,X)and 47,XYY can be reliably determined. The FISH analysis does not detect structural chromosome abnormalities,mosaicism, and other numerical chromosome abnormalities (excluding X, Y, 13, 18, and 21). In addition, falsepositiveor negative results, as well as maternal cell contamination, have been demonstrated in prenatal FISHanalysis. It is recommended (e.g. American College of Medical Genetics) that irreversible therapeutic actionshould not be initiated on the basis of FISH results alone.Trisomy 21 – Down SyndromeDown syndrome is caused by an extra chromosome 21. It isthe most common single cause of human birth defects, with anoccurrence in 1 out of every 660 births. Congenital heart defectsare frequently present in Down syndrome children. The normallife span mainly is shortened in Down syndrome by congenitalheart disease and by increased incidence of acute leukemia.Mental retardation is variable, and usually moderate. Someadults live independently and are accomplished individuals.Trisomy 13 – Patau SyndromeTrisomy 13, also called Patau syndrome, is a chromosomalcondition that is associated with severe mental retardationand certain physical abnormalities. Affected individualsrarely live past infancy because of the life-threateningmedical problems associated with this condition. Trisomy13 affects approximately 1 in 10,000 newborns. The risk ofhaving a child with trisomy 13 increases as a woman getsolder.The chromosome 21 specific region probe is optimized to detectcopy numbers of chromosome 21 at 21q22.1 on unculturedamniotic cells. In all PN combinations the 21q specific DNAprobe is direct-labeled in red with PlatinumBright550.The chromosome 13 specific region probe is optimized to detectcopy numbers of chromosome 13 at 13q14.2 on unculteredamniotic cells. In all PN combinations the 13q14 specific DNAprobe is direct-labeled in green with PlatinumBright495.Cat.# KBI-40002 PN 21 (21q22)Cat.# KBI-40001 PN 13 (13q14)RH 72110D13S1195Prenatal Probes2121q22.1DSCR1D21S65RH 92717360 KBPN 21 (21q22) probe hybridizedto a normal metaphase (2R).1313q14RB1D13S810900 KBPN 13 (13q14) probe hybridizedto a normal metaphase (2G).68

Trisomy 18 – Edward SyndromeTrisomy 18 is caused by an extra chromosome 18 and usuallyconsists of mental retardation, small birth size, and manydevelopmental anomalies, including severe microcephaly,prominent occiput, low-set malformed ears, and a characteristicpinched facial appearance. Trisomy 18 occurs 1 in 6000 livebirths, but spontaneous abortions are common. More than95% of affected children have complete trisomy 18. Theextra chromosome is almost always maternally derived, andadvanced maternal age increases risk.Cat.# KBI-20018-B SE 18 (D18Z1)Sex Chromosome AbnormalitiesChromosomal abnormalities involving the X and Y chromosome(sex chromosomes) are slightly less common than autosomalabnormalities and are usually much less severe in their effects.The high frequency of people with sex chromosome aberrationsis partly due to the fact that they are rarely lethal conditions.• Turner syndrome occurs when females inherit only one Xchromosome – their genotype is X0.• Metafemales or triple-X females, inherit three X chromosomes– their genotype is XXX or more rarely XXXX or XXXXX.• Klinefelter syndrome males inherit one or more extra Xchromosomes – their genotype is XXY or more rarely XXXY,XXXXY, or XY/XXY mosaic.• XYY syndrome males inherit an extra Y chromosome – theirgenotype is XYY.SE 18 (D18Z1) probe hybridized to a normal metaphaseshowing two blue signals (2B).The chromosome 18 specific Satellite Enumeration (SE 18)probe (D18Z1) is optimized to detect copy numbers ofchromosome 18 at 18p11-18q11 on uncultured amniotic cells.In all PN combinations the 18 SE centromeric DNA probe isoffered direct-labeled in blue with PlatinumBright415.Other combinationsThe chromosome X specific SE probe (DXZ1) is optimizedto detect copy numbers of chromosome X at Xp11-Xq11 onuncultured amniotic cells. The chromosome Y specific SE probe(DYZ3) is optimized to detect copy numbers of chromosomeY at Yp11-Yq11 on uncultured amniotic cells. In all PrenatalProbes combinations the X SE centromeric DNA probe is offereddirect-labeled in green with PlatinumBright495.Technical informationIn most Prenatal Probes combinations the Y SE centromeric DNAprobe is offered direct-labeled in red with PlatinumBright550,except for the KBI-40008 where the Y SE is labeled in blue withPlatinumBright415. All prenatal probes are in a Ready-to-Use formore convenience. This format still allows adding of a SE 18 probe.Ordering informationDescription Color Tests Cat#PN 13 (13q14) / 21 (21q22)probe hybridized to a normalinterphase (2R2G).PloidyScreen (21, X, Y) probehybridized to a normal malemetaphase (2R1G1B).PN 13 (13q14) green 10 KBI-40001PN 21 (21q22) red 10 KBI-40002PN 13 (13q14) / 21 (21q22) green/red 10 KBI-40003SE 18 (D18Z1) 5x conc blue 10 KBI-20018-BSE X (DXZ1) / SE Y (DYZ3) green/red 10 KBI-20030SE 7 (D7Z1) / SE 8 (D8Z1) red/green 10 KBI-20031SE (X,Y,18) green/red/blue 10 KBI-20032PrenatScreen (13/21, X/Y18) green/red/blue 10 KBI-40005PrenatScreen (13/21, X/Y18) green/red/blue 30 KBI-40006PrenatScreen (13/21, X/Y18) green/red/blue 50 KBI-40007PloidyScreen (21, X, Y) red/green/blue 20 KBI-40008Prenatal Probes69

Microdeletion probesMicrodeletion syndromes are usually caused by a chromosomal deletion spanning one or several genesthat are too small to be detected under the microscope using conventional cytogenetic methods.Depending on the size of the deletion, FISH or other methods of DNA analysis can be employed toidentify such deletions.Description Cat# PageMD Miller-Dieker LIS (17p13 ) / Smith-Magenis RAI (17p11) KBI-40101 77MD DiGeorge “N25” (22q11) / 22q13 (SHANK3) KBI-40102 71,73MD DiGeorge Tuple (22q11) / 22q13 (SHANK3) KBI-40103 72,73MD DiGeorge T-box1 (22q11) / 22q13 (SHANK3) KBI-40104 72,73MD DiGeorge II (10p14) / SE 10 KBI-40105 73MD Cri-Du-Chat CTNND (5p15) / 5q31 KBI-40106 78MD Wolf-Hirschhorn WHSC1 (4p16) / SE 4 KBI-40107 78MD X-Inactivation XIST (Xq13) / SE X KBI-40108 79Microdeletion ProbesMD Prader-Willi SNRPN (15q11) / PML(15q24) KBI-40109 75MD Angelman UBE3A (15q11) / PML(15q24) KBI-40110 76MD Williams-Beuren ELN (7q11) / 7q22 KBI-40111 76MD Short Stature (Xp22) / SE X KBI-40112 79MD NSD1 (5q35)/ hTERT (5p15) KBI-40113 74MD NF1 (17q11) / MPO (17q22) KBI-40114 74MD STS (Xp22) / KAL (Xp22) / SE X TC KBI-40115 8070MD IGF1R (15q26) / 15q11 KBI-40116 81

DiGeorge / Velocardiofacial Syndrome (VCFS)Microdeletion of chromosome 22 accounts for morethan 90% of cases of DiGeorge anomaly which hasan incidence of 1 in 4000 live births. Deletionsof chromosome 22q11.2 are found in the vastmajority of patients with DiGeorge anomaly andVCFS. Most deletions are de novo, with 10% or lessinherited from an affected parent. All probes thatare currently in use to detect deletions in DiGeorgeand VCFS are located within the described minimalcritical region of 1.5 Mb.MD DiGeorge “N25” (22q11) / 22q13 (SHANK3)The DiGeorge “N25” probe was the first commercialmicrodeletion probe for chromosome 22q and detects the locusD22S75. This marker is located between DGCR2 and CLH22(Clathrin). Both genes have been extensively investigated andtheir role in DiGeorge syndrome is well established.The DiGeorge ”N25” region probe covers the marker “N25”(D22S75) and adjacent region of CLH22 (Clathrin gene region)and DGCR2 (DiGeorge critical region gene 2). The SHANK3probe at 22q13 is serving as internal control.Cat.# KBI-40102 MD DiGeorge “N25” (22q11) / 22q13 (SHANK3)D22S1660DGCR2"N25"250 KBCLH22D22S164622q11.2D22S55322TUPLERH845722q13ARSASHANK3130 KBRH38881MD DiGeorge "N25" (22q11) / 22q13 (SHANK3) probe hybridized toa normal metaphase (2R2G).Literature:Sirotkin et al, 1996, Hum Mol Genet, 5: 617-624.Holmes et al, 1997, Hum Mol Genet, 6: 357-367.Wilson, et al, 2003, J Med Genet 40; 575-584Luciani, et al, 2003, J Med Genet 40; 690-696Ordering information Gene Region Tests Cat#MD DiGeorge “N25” (22q11) / 22q13 (SHANK3) N25 10 KBI-40102Microdeletion Probes71

MD DiGeorge “TUPLE” (22q11) / 22q13 (SHANK3)The DiGeorge “Tuple” probe targets a putative transcriptionalregulator (TUPLE1 or HIRA, HIR histone cell cycle regulationdefective homolog A) which also has been identified to liewithin the commonly deleted region DiGeorge syndrome.This probe is located distally to the “N25” probe. TheDiGeorge “Tuple” region probe is optimized to detect copynumbers of the Tuple (Hira) gene region at 22q11.2.The SHANK3 probe at 22q13 is serving as internal control.MD DiGeorge T-Box1 (22q11) / 22q13 (SHANK3)The 22q11 deletion in DiGeorge syndrome/VCFS ischaracterized by defects in the derivatives of the pharyngealapparatus. TBX1, a member of the T-box transcriptionfactor family, is required for normal development of thepharyngeal arch arteries. Haploinsufficiency of TBX1 hasbeen demonstrated to be sufficient to generate at least oneimportant component of the DiGeorge syndrome phenotypein mice. The TBX1 is also located within the minimal criticalDiGeorge region in humans.The DiGeorge TBX1 region probe is optimized to detectcopy numbers of the TBX1 gene region at 22q11.2. Thesubtelomeric (ST) 22qter DNA probe is included as controlprobe. The SHANK3 probe at 22q13 is serving as internalcontrol.Cat.# KBI-40103 DiGeorge “Tuple” (22q11) / 22q13 (SHANK3)Cat.# KBI-40104 MD DiGeorge T-box1 (22q11) / 22q13 (SHANK3)DGCR2"N25"TUPLECLH2222q11.2D22S55322q11.2D22S1624D22S163722TUPLED22S1668220 KB22TBX1RH82134230 KBRH845722q13ARSARH845722q13ARSA130 KB130 KBSHANK3SHANK3RH38881RH38881Microdeletion ProbesMD DiGeorge "Tuple" (22q11) / 22q13 (SHANK3) probe hybridizedto a normal metaphase (2R2G).Literature:Lorain at al, 1996, Genome Res, 6: 43-50.Ordering information Gene Region Tests Cat#MD DiGeorge Tuple (22q11) / 22q13 (SHANK3) TUPLE 10 KBI-40103MD DiGeorge T-box1 (22q11) / 22q13 (SHANK3) probehybridized to DiGeorge patient material showing a deletion ofthe TBX1 gene region at 22q11 (1R2G).Image kindly provided by Dr F Girard-Lemaire Service de Cytogénétique (Dr Flori), CHU StrasbourgLiterature:Lindsay et al, 2001, Nature, 410: 97-101.Merscher et al, 2001, Cell, 104: 619-629.Paylor et al, 2006, PNAS, 103: 7729-7734.Ordering information Gene Region Tests Cat#MD DiGeorge T-box1 (22q11) / 22q13 (SHANK3) TBX1 10 KBI-4010472

Phelan-McDermid SyndromeThe 22q13 deletion syndrome (or Phelan-McDermidsyndrome) is characterized by moderate to profoundmental retardation, delay/absence of expressivespeech, hypotonia, normal to accelerated growth,and mild dysmorphic features. A terminal deletionincluding the SHANK3 gene region has been identifiedfor this syndrome.MD DiGeorge (22q11) / 22q13 (SHANK3)The 22q13 DNA probe is optimized to detect copy numbersof the SHANK3 gene region at 22q13. The DiGeorge regionprobe at 22q11 is serving as internal control.MD DiGeorge II (10p14) / SE 10DiGeorge and VCFS present many clinical problems and arefrequently associated with deletions within 22q11.2 (seeprevious probes), but a number of cases have no detectablemolecular defect of this region. A number of single casereports with deletions of 10p suggest genetic heterogeneityof DiGeorge syndrome. FISH analysis demonstrates that thesepatients have overlapping deletions at the 10p13/10p14boundary. The shortest region of deletion overlap (SRO) hasbeen identified in a 1 cM interval including makers D10S547and D10S585.The DiGeorge II region probe is optimized to detect copynumbers of the DGCRII (DiGeorge critical region gene 2)at 10p14. The chromosome 10 satellite enumeration (SE10) probe at D10Z1 is included to facilitate chromosomeidentification.Cat.# KBI-40105 MD DiGeorge II (10p14) / SE 1010p14D10Z1D10S547RH-112076DGCR2350 KBRH66174WI-945210MD DiGeorge T-box1 (22q11) / 22q13 (SHANK3) probehybridized to patient material showing a deletion ofthe SHANK3 region at 22q13 (2R1G).Literature:Wilson, et al, 2003, J Med Genet 40; 575-584.Luciani, et al, 2003, J Med Genet 40; 690-696.Ordering information Gene Region Tests Cat#MD DiGeorge “N25” (22q11) / 22q13 (SHANK3) N25 10 KBI-40102MD DiGeorge Tuple (22q11) / 22q13 (SHANK3) TUPLE 10 KBI-40103MD DiGeorge T-box1 (22q11) / 22q13 (SHANK3) TBX1 10 KBI-40104MD DiGeorge II(10p14) / SE 10 probe hybridized toDiGeorge II patient material showing a deletion of the DGCRIIgene region at 10p14 (1R2G).Imaqe kindly provided by Azzedine Aboura, Hôpital Robert Debré ParisLiterature:Monaco et al, 1991, Am J Med Genet, 39: 215-216.Schuffenhauer et al, 1998, Eur J Hum Genet, 6: 213-225.Ordering information Gene Region Tests Cat#MD DiGeorge II (10p14) / SE 10 10p- 10 KBI-40105Microdeletion Probes73

MD NSD1 (5q35) / hTERT (5p15)NSD1 microdeletions (chromosome 5q35) are the majorcause of Sotos syndrome, and occur in some cases of Weaversyndrome. Sotos is a childhood overgrowth characterizedby distinctive craniofacial features, advanced bone age, andmental retardation. Weaver syndrome is characterized by thesame criteria but has its own specific facial characteristics.Sotos syndrome is inherited in an autosomal dominant manner.While 50% of Sotos patients in Asia are showing a chromosomalmicrodeletion, only 9% deletion cases are observed in theaffected European population.The NSD1 (5q35) region probe is optimized to detect copynumbers of the NSD1 gene region at 5q35.2. The hTERT regionspecific DNA probe at 5p15 is included as control probe.MD NF1 (17q11) / MPO (17q22)NF1, or von Recklinghausen disease, is one of the most commonhereditary neurocutaneous disorders in humans and one ofthe most common single gene syndromes. Clinically, NF1 ischaracterized by café-au-lait spots, freckling, skin neurofibroma,plexiform neurofibroma, bone defects, Lisch nodules andtumors of the central nervous system. The responsible gene,NF1 (neurofibromin), was identified on chromosome 17q11.Whole NF1 gene deletions occur in 4%-5% of individuals withNF1 and can be detected by FISH analysis.The NF1 (17q11) region probe is optimized to detect copynumbers of the NF1 gene region at 17q11.2.The MPO region specific DNA probe at 17q22 is included ascontrol probe.Cat.# KBI-40113 NSD1 (5q35) / hTERT (5p15)Cat.# KBI-40114 NF1 (17q11) / MPO (17q22)5p15.3D5S1981D17S1307NF1420 KBhTERT190 KBD5S226917q11RH25868D5S27031717q225q35NSD1320 KBD17S21515D5S1624EMPO400 KBSHGC-144222Microdeletion ProbesNSD1 (5q35) / hTERT (5p15) probehybridized to a normal metaphase(2R2G).Literature:Douglas et al, 2003, Am. J. Hum. Genet. 72; 132-143Rio et al, 2003, J. Med. Genet. 40; 436-440NSD1 (5q35) / hTERT (5p15) probehybridized to patient materialshowing a microdeletion of theNSD1 gene region at 5q35 (1R2G).Ordering information Gene Region Tests Cat#MD NSD1 (5q35) / hTERT (5p15) NSD1 10 KBI-40113NF1 (17q11) / MPO (17q22) probe hybridized topatient material showing a deletion of NF1 gene regionat 17q11 (1R2G).Literature:Riva P et al, 2000, Am.J.Hum.Genet. 66; 100-109Dorschner et al, 2000, Hum.Mol.Genet. 9; 35-46Ordering information Gene Region Tests Cat#MD NF1 (17q11) / MPO (17q22) NF1 10 KBI-4011474

Prader-Willi/Angelman SyndromePrader-Willi syndrome (PWS) and Angelmansyndrome (AS) are clinically distinct complexdisorders mapped to chromosome 15q11-q13. Theyboth have characteristic neurologic, developmental,and behavioral phenotypes plus other structural andfunctional abnormalities. However, the cognitiveand neurologic impairment is more severe inAS, including seizures and ataxia. The behavioraland endocrine disorders are more severe in PWS,including obsessive-compulsive symptoms andhypothalamic insufficiency. Both disorders canresult from microdeletion, uniparental disomy, oran imprinting center defect in 15q11-q13.MD Prader-Willi SNRPN (15q11) / PML (15q24)Prader-Willi syndrome (PWS) is a clinically distinct disorderincluding diminished fetal activity, obesity, hypotonia, mentalretardation, short stature, hypogonadotropic hypogonadism,strabismus, and small hands and feet.Approximately 70% of cases of PWS arise from paternaldeletion of the 15q11-q13 region including the gene SNRPN(small nuclear ribonucleoprotein polypeptide N). The PWSSNRPN region probe is optimized to detect copy numbers ofthe SNRPN gene region at 15q11. The PML (promyelocyticleukemia) gene specific DNA probe at 15q24 is included ascontrol probe.Cat.# KBI-40109 Prader-Willi SNRPN (15q11) / PML (15q24)D15S677SNRPN220 KBD15S631E15q11.2UBE3AD15S101515q24RH 54241PML200 KBD15S991Prader-Willi SNRPN (15q11) / PML (15q24) probe hybridized to anormal interphase/metaphase (2R2G).Literature:Knoll et al, 1989, Am J Med Genet, 32: 285-290.Ozcelik et al, 1992, Nat Genet, 2: 265-269.Ordering information Gene Region Tests Cat#MD Prader-Willi SNRP (15q11) PML (15q24) SNRPN 10 KBI-40109Microdeletion Probes75

MD Angelman UBE3A (15q11) / PML (15q24)Angelman syndrome (AS) is characterized by severedevelopmental delay or mental retardation, severe speechimpairment, gait ataxia and/or tremulousness of the limbs,and an unique behavior with an inappropriate happydemeanor that includes frequent laughing, smiling, andexcitability. In addition, microcephaly and seizures arecommon. AS is caused by absence of a maternal contributionto the imprinted region on chromosome 15q11-q13 includingthe UBE3A gene.The AS UBE3A region probe is optimized to detect copynumbers of the UBE3A gene region at 15q11. The PML(promyelocytic leukemia) gene specific DNA probe at 15q24is included as control probe.MD Williams-Beuren ELN (7q11) / 7q22Williams-Beuren syndrome (WS) is characterized bycardiovascular disease, distinctive facial features, connectivetissue abnormalities, mental retardation and endocrineabnormalities. Over 99% of individuals with the clinical diagnosisof WS have this contiguous gene deletion, that encompassesthe elastin (ELN) gene region including ELN, LIMK1, and theD7S613 locus.The Williams-Beuren region probe is optimized to detect copynumbers of the ELN gene region at 7q11. The 7q22 regionspecific DNA probe at 7q22 is included as control probe.Cat.# KBI-40110 Angelman UBE3A (15q11) / PML (15q24)Cat.# KBI-40111 Williams-Beuren ELN (7q11) / 7q22SNRPNSWSS2677ELND15S108915q11.2UBE3AD15S10D15S210220 KB7q22LIMK17q11.2CYLN2350 KB1515q24RH 54241D7S3272PML7200 KBD15S991Microdeletion ProbesAngelman UBE3A (15q11) / PML (15q24) probe hybridized to anormal interphase/metaphase (2R2G).Literature:Matsuura et al, 1997, Nat Genet, 15: 74-77.Burger et al, 2002, Am J Med Genet, 111: 233-237.Ordering information Gene Region Tests Cat#MD Angelman UBE3A (15q11) / PML (15q24) UBE3A 10 KBI-40110Williams-Beuren ELN (7q11) / 7q22 probe hybridized to anormal metaphase (2RG).Literature:Ewart, et al, 1993, Nat Genet, 5: 11-16.Botta et al, 1999, J Med Genet, 36: 478-480Ordering information Gene Region Tests Cat#MD Williams-Beuren ELN (7q11) / 7q22 ELN 10 KBI-4011176

MD Miller-Dieker LIS (17p13) / Smith-MagenisRAI (17p11)Miller-Dieker Syndrome (MDS) is characterized by classicallissencephaly and distinct facial features. The lissencephalyrepresents the severe end of the spectrum with generalizedagyria or agyria with some frontal pachygyria. Submicroscopicdeletions of 17p13.3 including the LIS1 (now calledPAFAH1B1, platelet-activating factor acetylhydrolase) geneare found in almost 100% of patients.The Miller-Dieker region probe is optimized to detect copynumbers of the PAFAH1B1 gene (LIS1) region at 17p13.3.The Smith-Magenis RAI1 region probe at 17p11.2 is servingas internal control.Smith-Magenis Syndrome (SMS) is characterized by distinctivefacial features that progress with age, developmentaldelay, cognitive impairment, and behavioral abnormalities.Molecular cytogenetic analysis by FISH using a DNA probespecific for the SMS critical region is recommended in casesof submicroscopic deletions and/or to resolve equivocalcases. RAI1 is the only gene known to account for a majorityof features in SMS. All 17p11.2 deletions associated withSMS include a deletion of RAI1.The Smith-Magenis region probe is optimized to detectcopy numbers of the RAI1 gene region involved in Smith-Magenis syndrome at 17p11.2. The Miller-Dieker LIS1 probeat 17p13.3 is serving as internal control.Cat.# KBI-40101 Miller-Dieker LIS (17p13) / Smith-Magenis RAI (17p11)RH34464PAFAH1B117p13.3D17S1583D17S1682350 KBD17S15811717p11.2RH122147RAI1250 KBRH68538D17S447FLI1Miller-Dieker LIS (17p13) / Smith-Magenis RAI (17p11) probehybridized to a normal metaphase (2RG).Literature:Kuwano et al, 1991, Am J Hum Genet, 49: 707-714.Cardoso et al, 2003, Am J Hum Genet, 72: 918-930.Miller-Dieker LIS (17p13) / Smith-Magenis RAI (17p11) probehybridized to Smith-Magenis patient material showing a deletion ofthe RAI1 gene region at 17p11 (2R1G).Image kindly provided by Prof Jauch, Heidelberg.Literature:Smith et al, 1986, Am J Med Genet, 24: 393-414.Greenberg et al, 1991, Am J Med Genet, 49: 1207-1218.Vlangos et al, 2005, Am J Med Genet, 132: 278-282.Ordering information Gene Region Tests Cat#MD Miller-Dieker LIS (17p13) / Smith-MagenisRAI (17p11)LIS1/RAI1 10 KBI-40101Microdeletion Probes77

MD Wolf-Hirschhorn WHSC1 (4p16)Wolf-Hirschhorn syndrome (WHS) affected individuals haveprenatal-onset growth deficiency followed by postnatal growthretardation and hypotonia with muscle under-development.Developmental delay/mental retardation of variable degreeis present in all. FISH analysis using a WHSC1 specific probefor chromosomal locus 4p16.3 detects more than 95% ofdeletions in WHS.The Wolf-Hirschhorn region probe is optimized to detect copynumbers of the Wolf-Hirschhorn critical region at 4p16. Thechromosome 4 satellite enumeration (SE 4) probe at D4Z1 isincluded to facilitate chromosome identification.MD Cri-Du-Chat CTNND (5p15) / 5q31Cri-Du-Chat syndrome is an autosomal deletion syndromecaused by a partial deletion of chromosome 5p. It ischaracterized by a distinctive, high-pitched, catlikecry in infancy with growth failure, microcephaly, facialabnormalities, and mental retardation throughout life. Lossof a small region in band 5p15.2 (Cri-Du-Chat critical region)correlates with all the clinical features of the syndrome withthe exception of the catlike cry, which maps to band 5p15.3(catlike cry critical region).The Cri-Du-Chat region probe is optimized to detect copynumbers at the CTNND2 gene region in the Cri-Du-Chatcritical region at 5p15.2. The 5q31 specific DNA probe isincluded as control probe.Cat.# KBI-40107 Wolf-Hirschhorn WHSC1 (4p16) / SE 4Cat.# KBI-40106 Cri-Du-Chat CTNND (5p15) / 5q31D4Z14p16RH181375p15.2D5S117D4S114WHSC1D4S166120 KB5q31CTNND2RH121454SH6C-153474D5S2874580 KB45Oncology Microdeletion probes ProbesWolf-Hirschhorn WHSC1 (4p16) / SE 4 probe hybridized to Wolf-Hirschhorn patient material showing a deletion of the WHSC1 generegion at 4p16 (1R2G).Image kindly provided by Prof Zollino, RomeLiterature:Gandelman et al, 1992, Am J Hum Genet, 51: 571-578.Wright et al, 1997, Hum Mol Genet, 6: 317-324.Ordering information Gene Region Tests Cat#MD Wolf-Hirschhorn WHSC1 (4p16) / SE 4 WHSC1 10 KBI-40107Cri-Du-Chat CTNND (5p15) / 5q31 probe hybridized to a normalmetaphase (2R2G).Literature:Overhauser et al, 1994, Hum Mol Genet, 3: 247-252.Gersh et al, 1997, Cytogenet Cell Genet, 77: 246-251.Ordering information Gene Region Tests Cat#MD Cri-Du-Chat CTNND (5p15) / 5q31 5p- 10 KBI-4010678

MD X-Inactivation XIST (Xq13) / SE XThe XIST locus is expressed only from the inactive Xchromosome, resides at the putative X inactivation centre,and is considered a prime player in the initiation ofmammalian X dosage compensation. The severe phenotypeof human females whose karyotype includes tiny ring Xchromosomes has been attributed to the inability of thesmall ring X chromosome to inactivate. Many of the ringchromosomes lack the XIST locus, consistent with XISTbeing necessary for cis inactivation.The XIST specific DNA probe is optimized to detect copynumbers of the XIST region at Xq13. The chromosome Xsatellite enumeration (SE X) probe at DXZ1 is added tofacilitate chromosome identification.MD Short Stature (Xp22) / SE XIndividuals with SHOX-related short stature havedisproportionate short stature and/or wrist abnormalitiesconsistent with those described in Madelung deformity. TheSHOX genes located on the pseudoautosomal regions ofthe X and Y chromosomes are the only genes known to beassociated with SHOX-related haploinsufficiency.The SHOX region probe is optimized to detect copy numbersof the SHOX gene region at Xp22. The chromosome X satelliteenumeration (SE X) probe at DXZ1 is added to facilitatechromosome identification.Cat.# KBI-40108 X-Inactivation XIST (Xq13) / SE XCat.# KBI-40112 Short stature (Xp22) / SE XDXS1677CHIC1Xp22.3DXZ1RH47603DXZ1DXYS153Xq13.2XIST290 KBSHOXDXYS130190 KBDXS8235XDXS1166XX-Inactivation XIST (Xq13) / SE X probe hybridized to a malemetaphase (1R1G).Literature:Migeon et al, 1993, PNAS, 90: 12025-12029.Jani et al, 1995, Genomics, 27: 182-188.Ordering information Gene Region Tests Cat#MD X-Inactivation XIST (Xq13) / SE X XIST 10 KBI-40108Short stature (Xp22) / SE X probe hybridized to a malemetaphase (2R1G).Literature:Rao et al, 1997, Hum Genet, 100: 236-239.Morizio et al, 2003, Am J Med Genet, 119: 293-296.Ordering information Gene Region Tests Cat#MD Short Stature (Xp22) / SE X SHOX 10 KBI-40112Oncology Microdeletion probes Probes79

MD STS (Xp22) / KAL (Xp22) / SE X TCSTS (Steroid Sulfatase) disease is a chromosome X-linkeddisorder associated with a microdeletion of the gene withinthe Xp22.3 region. Deletion of the steroid sulfatase genehas been detected in individuals with recessive X-linkedichtyosis, the disease been considered one of the mostfrequent human enzyme deficient disorders. KAL1 (Kallmannsyndrome interval gene-1) maps to the Kallmann syndromecritical region on the distal short arm of the human Xchromosome. Individuals with Kallmann syndrome suffers ofhypogonadotropic hypogonadism and anosmia, with clinicalfeatures of variable phenotype. It affects approximately 1 in8000 males and 1 in 40000 females.The STS (Xp22) region probe is optimized to detect copynumbers of the STS gene region at Xp22. The KAL (Xp 22)region probe is optimized to detect copy numbers of theKAL gene region at Xp22. The Chromosome X SatelliteEnumeration (SE X) probe at DXZ1 is included to facilitatechromosome identification.Cat.# KBI-40115 STS (Xp22) / KAL (Xp22) / SE X TCDXS1130Xp22STS390 KBDXZ1RH66689Gap: 1 MBDXS1223KAL325 KBDXS7716XMicrodeletion ProbesSTS (Xp22) / KAL (Xp22) / SE X TC probe hybridized to male patientmaterial showing a deletion of the STS gene region (1R1B).Material kindly provided by Necker hospital, ParisLiterature:Alper in et al, 1997, J. Biol. Chem 272; 20756-20763.Meroni et al, 1996, Hum. Mol. Genet. 5; 423-431Ordering information Gene Region Tests Cat#MD STS (Xp22) / KAL (Xp22) / SE X TC STS/KAL 10 KBI-4011580

MD IGF1R (15q26) / 15q11Congenital diaphragmatic hernia (CDH) is a severe, lifethreatening,congenital anomaly characterized by variabledefect in the diaphragm, pulmonary hypoplasia, and postnatalpulmonary hypertension. Deletion of the IGF1R (insulin-likegrowth factor 1 receptor) gene region at 15q25 is the mostfrequent anomaly found in CDH. The type 1 IGF receptorat 15q26 is required for normal embryonic and postnatalgrowth. Deletions, but also gain of an approximately 5 Mbregion including the IGF1R gene has been found to have aprofound effect on prenatal and early postnatal growth.The IGF1R (15q26) specific probe is optimized to detect copynumbers of the IGF1R gene region at region 15q26. The15q11 (SNRPN / UBE3A) specific region probe is included tofacilitate chromosome identification.Cat.# KBI-40116 IGF1R (15q26) / 15q11RH54346SNRPN900 KB15q11UBE3AD15S1015 15q26SHGC 154952IGF1R530 KBRH294IGF1R (15q26) / 15q11 probe hybridized to patient materialshowing a deletion of the IGF1R gene region at 15q26 (1R2G).Literature:Faivre et al, 2002, Eur J Hum Genet. 10 ; 699-706.Okubo et al, 2003, J Clin Endocrinol. Metab 88 ; 5981-5988Ordering information Gene Region Tests Cat#MD IGF1R (15q26) / 15q11 IGF1R 10 KBI-40116Microdeletion Probes81

Sub-Telomere probesTelomeres are specialized DNA-protein structures containing long stretches of (TTAGGG)n repeats at the end of allchromosomes. They protect chromosomes from degradation and end-to-end fusion with other chromosomes.The region adjacent to sequences containing telomeric repeats is called the sub-telomer which has been foundto be relative gene-rich. Cytogenetic analysis of sub-telomeric regions is difficult due to low resolution usingconventional banding techniques. Cryptic deletions and rearrangements have been associated with unexplainedmental retardation and congenital abnormalities.FISH probes specific for the sub-telomeric regions of the terminal chromosome regions are essential to detectsuch subtle rearrangements.ST - Sub-Telomeric probesDual-Color(TTAGGG)nrepeatsDistalsub-telomericsequenceDegenerate (TTAGGG)nSub-Telomere probes 6pter and 2pter showing trisomyof tel 6p and monosomy of tel 2p.Image kindly provided by Institute Pasteur, Paris.Triple-ColorProximalsub-telomericsequenceSub-Telomere Probes82ChromosomeuniquesequenceTechnical information:The ST probes are supplied in a 5 test format together withhybridization buffer, labeled in green (PlatinumBright495), red(PlatinumBright550), or blue (PlatinumBright415).Combination of Sub-Telomere probes 6qter (red),8qter (green) and 9pter (blue)Poseidon ST probes are provided in concentrated format toallow, mixing of up to 5 ST probes in a single hybridizationassay. Please refer to the Instruction for Use Manual for furtherdetails.Note:All probes in the ST range have not shown any cross-hybridization to other chromosomalregions. However, it cannot be excluded that certain sequence polymorphism could stillexist. If any unusual hybridization patterns are observed please contact us

Product and ordering informationLocation Marker Probe Size (kb) Distance from telomere (kb) Color Tests Cat.# *Sub-Telomere 1pter D1S2217 170 800 red, green or blue 5 KBI-40201Sub-Telomere 1qter D1S555 170 350 red, green or blue 5 KBI-40202Sub-Telomere 2pter D2S2147 210 300 red, green or blue 5 KBI-40203Sub-Telomere 2qter D2S2142 185 800 red, green or blue 5 KBI-40204Sub-Telomere 3pter D3S4558 175 450 red, green or blue 5 KBI-40205Sub-Telomere 3qter D3S4168 170 900 red, green or blue 5 KBI-40206Sub-Telomere 4pter D4S3360 180 100 red, green or blue 5 KBI-40207Sub-Telomere 4qter D4S2283 190 700 red, green or blue 5 KBI-40208Sub-Telomere 5pter D5S2488 175 180 red, green or blue 5 KBI-40209Sub-Telomere 5qter D5S2006 270 600 red, green or blue 5 KBI-40210Sub-Telomere 6pter RH40931 110 350 red, green or blue 5 KBI-40211Sub-Telomere 6qter D6S2523 165 250 red, green or blue 5 KBI-40212Sub-Telomere 7pter D7S2644 220 850 red, green or blue 5 KBI-40213Sub-Telomere 7qter D7S427 180 200 red, green or blue 5 KBI-40214Sub-Telomere 8pter RH65733 180 550 red, green or blue 5 KBI-40215Sub-Telomere 8qter D8S595 210 200 red, green or blue 5 KBI-40216Sub-Telomere 9pter D9S917 190 450 red, green or blue 5 KBI-40217Sub-Telomere 9qter D9S1838 185 500 red, green or blue 5 KBI-40218Sub-Telomere 10pter D10S2488 180 350 red, green or blue 5 KBI-40219Sub-Telomere 10qter D10S2290 230 350 red, green or blue 5 KBI-40220Sub-Telomere 11pter D11S1363 155 1050 red, green or blue 5 KBI-40221Sub-Telomere 11qter D11S4437 170 300 red, green or blue 5 KBI-40222Sub-Telomere 12pter D12S158 185 150 red, green or blue 5 KBI-40223Sub-Telomere 12qter D12S399 190 180 red, green or blue 5 KBI-40224Sub-Telomere 13qter D13S1160 190 90 red, green or blue 5 KBI-40225Sub-Telomere 14qter D14S1419 170 250 red, green or blue 5 KBI-40226Sub-Telomere 15qter RH54179 150 250 red, green or blue 5 KBI-40227Sub-Telomere 16pter D16S521 150 40 red, green or blue 5 KBI-40228Sub-Telomere 16qter RH25942 180 240 red, green or blue 5 KBI-40229Sub-Telomere 17pter D17S643 110 80 red, green or blue 5 KBI-40230Sub-Telomere 17qter D17S724 70 500 red, green or blue 5 KBI-40231Sub-Telomere 18pter D18S1244 180 200 red, green or blue 5 KBI-40232Sub-Telomere 18qter D18S1390 220 160 red, green or blue 5 KBI-40233Sub-Telomere 19pter D19S814 220 550 red, green or blue 5 KBI-40234Sub-Telomere 19qter D19S989 160 300 red, green or blue 5 KBI-40235Sub-Telomere 20pter D20S1156 240 180 red, green or blue 5 KBI-40236Sub-Telomere 20qter RH44234 170 350 red, green or blue 5 KBI-40237Sub-Telomere 21qter D21S1446 190 80 red, green or blue 5 KBI-40238Sub-Telomere 22qter D22S1056 200 850 red, green or blue 5 KBI-40239Sub-Telomere XYpter DXYS130 180 400 red, green or blue 5 KBI-40240Sub-Telomere XYqter DXYS224 160 70 red, green or blue 5 KBI-40241Sub-Telomere Probes* Add -G for Green, -R for Red, -B for Blue (available on request)83

Satellite Enumeration probesThe primary constriction, called the centromer, is a common feature of chromosomes necessary for cell division.Presence of repetitive sequences in the centromeric regions have been proven to be essential. In humans, andmany other species, specific repetitive sequences, called ‘Satellites’ are characteristic for the centromer ingeneral. Most chromosomes have even repetitive sequences which are specific for individual chromosomes andcan be used for precise identification and enumeration of human chromosomes in metaphase and interphasecells. The Poseidon Satellite Enumeration probes – SE – allow rapid and specific chromosome analysis, markerchromosome identification and the detection of aneuploidy. Essentially, these probes can be used in all aspectsof routine work in genetics and oncology/pathology. Due to the sharp and bright signals produced, the Satelliteprobes can easily be used on various sample types, such as cultured cells, touch preparations buccal smears,cytospins, frozen and paraffin-embedded tissue sections, sputum samples, sperm samples, and bladder washes.Cat# KBI-20012-R Cat# KBI-20018-B Cat# KBI-20031 Cat# KBI-20030Satellite Enumeration ProbesAll Human Centromere (AHC) probeThis probe specifically hybridizes to the centromericregion of all human chromosomes, and is labeled withhigh fluorescence intensity in red or green color. PoseidonAHC probe is ideal for studying numerical chromosomeaberrations, studying aneuploidy, polyploidy, dicentrics,tricentrics, and other complex aberrations. It can also beused for general numerical chromosome analysis. PoseidonAHC probe is for RUO and is not meant to be used formedical purposes or as a diagnostic tool.Cat.# KBI-20000 All Human Centromere (AHC) probeTechnical information:All SE probes are supplied in a 10 test format together withhybridization buffer, labeled in green (PlatinumBright495),red (PlatinumBright550), or blue (PlatinumBright415).The SE combinations are already supplied in a dual-colorformat Ready-to-Use. Poseidon SE probes are provided inconcentrated format to allow, mixing of up to 5 SE probesin a single hybridization assay. Please refer to the Instructionfor Use Manual for further details.Note:Satellite sequences share some degree of homology between the sequences fromchromosome to chromosome. Therefore the recommended stringency conditions inhybridization and posthybridization washes must be followed to provide optimal results.Chromosomes 1/5/19, 13/21, and 14/22 share the same repetitive sequences andcannot be differentiated by chromosome specific repeats.84Cat.# KBI-20000

Product and ordering informationDescription Chromosome Color DNA Class Tests Cat.# *SE 1 (1qh) 1, 1qh red, green or blue Satellite III 10 KBI-20001SE 2 (D2Z2) 2 red, green or blue α-satellite 10 KBI-20002SE 3 (D3Z1) 3 red, green or blue α-satellite 10 KBI-20003SE 4 (D4Z1) 4 red, green or blue α-satellite 10 KBI-20004SE 6 (D6Z1) 6 red, green or blue α-satellite 10 KBI-20006SE 7 (D7Z1) 7 red, green or blue α-satellite 10 KBI-20007SE 8 (D8Z1) 8 red, green or blue α-satellite 10 KBI-20008SE 9 (classical) 9, 9qh red, green or blue Satellite III 10 KBI-20009SE 10 (D10Z1) 10 red, green or blue α-satellite 10 KBI-20010SE 11 (D11Z1) 11 red, green or blue α-satellite 10 KBI-20011SE 12 (D12Z3) 12 red, green or blue α-satellite 10 KBI-20012SE 15 (D15Z4) 15 red, green or blue α-satellite 10 KBI-20015SE 16 (D16Z2) 16 red, green or blue α-satellite 10 KBI-20016SE 17 (D17Z1) 17 red, green or blue α-satellite 10 KBI-20017SE 18 (D18Z1) 18 red, green or blue α-satellite 10 KBI-20018SE 20 (D20Z1) 20 red, green or blue α-satellite 10 KBI-20020SE X (DXZ1) X red, green or blue α-satellite 10 KBI-20023SE Y (DYZ3) Y, centromeric red, green or blue α-satellite 10 KBI-20024SE Y classical (DYZ1) Y, Yqh red, green or blue Satellite III 10 KBI-20025SE 1/5/19 (D1Z7) (D5Z2) (D19Z3) 1, 5, 19 red, green or blue α-satellite 10 KBI-20026SE 13/21 (D13Z1) (D21Z1) 13 and 21 red, green or blue α-satellite 10 KBI-20027SE 14/22 (D14Z1) (D22Z1) 14 and 22 red, green or blue α-satellite 10 KBI-20028SE combinationsSE X (DXZ1) / SE Y (DYZ3) RtU X and Y green/red α-satellite 10 KBI-20030SE 7 (D7Z1) / SE 8 (D8Z1) RtU 7 and 8 red/green α-satellite 10 KBI-20031AHC probe All Human Centromere red or green 10 KBI-20000* Add -G for Green, -R for Red, -B for Blue (available on request)Satellite Enumeration Probes85

Whole Chromosome probesThe Poseidon Whole Chromosome probes hybridize to unique sequences spanning the entire length of thetarget chromosome.These probes are derived from flow-sorted or microdissected chromosomes and provide accurate coveragewith excellent signal specificity and high fluorescent intensity. Some minor cross-hybridization may occurat the short arm of acrocentric chromosomes (13, 14, 15, 21 and 22) and in the pseudo-autosomal regions ofchromosome X and Y.The WC probes are used for identifying whole human chromosomes, analysis of translocation events,chromosome rearrangement studies and determining the origin of marker chromosomes. Mutagenesis analysis,radiation and sensitivity testing, and identification of human chromosomes on hybrid cells are investigatedusing these probes.KBI-30013-RWC Dual-ColorWhole Chromosome Probes86KBI-30023-GTechnical information:The WC probes are supplied in a 5 test format together withhybridization buffer, labeled in green (PlatinumBright495),red (PlatinumBright550) or in blue (PlatinumBright415).WC Triple-ColorPoseidon WC probes are provided in concentrated format toallow, mixing of up to 5 WC probes in a single hybridizationassay. Please refer to the Instruction for Use Manual forfurther details.Note:Due to decondensation of chromosomal DNA signals on interphase, cells can be verydiffuse. We therefore recommend not to use WC probes for interphase FISH.

Product and ordering informationDescription Chromosome Color Tests Cat.# *Whole Chromosome 1 Chromosome 1 Paint Red, green or blue 5 KBI-30001Whole Chromosome 2 Chromosome 2 Paint Red, green or blue 5 KBI-30002Whole Chromosome 3 Chromosome 3 Paint Red, green or blue 5 KBI-30003Whole Chromosome 4 Chromosome 4 Paint Red, green or blue 5 KBI-30004Whole Chromosome 5 Chromosome 5 Paint Red, green or blue 5 KBI-30005Whole Chromosome 6 Chromosome 6 Paint Red, green or blue 5 KBI-30006Whole Chromosome 7 Chromosome 7 Paint Red, green or blue 5 KBI-30007Whole Chromosome 8 Chromosome 8 Paint Red, green or blue 5 KBI-30008Whole Chromosome 9 Chromosome 9 Paint Red, green or blue 5 KBI-30009Whole Chromosome 10 Chromosome 10 Paint Red, green or blue 5 KBI-30010Whole Chromosome 11 Chromosome 11 Paint Red, green or blue 5 KBI-30011Whole Chromosome 12 Chromosome 12 Paint Red, green or blue 5 KBI-30012Whole Chromosome 13 Chromosome 13 Paint Red, green or blue 5 KBI-30013Whole Chromosome 14 Chromosome 14 Paint Red, green or blue 5 KBI-30014Whole Chromosome 15 Chromosome 15 Paint Red, green or blue 5 KBI-30015Whole Chromosome 16 Chromosome 16 Paint Red, green or blue 5 KBI-30016Whole Chromosome 17 Chromosome 17 Paint Red, green or blue 5 KBI-30017Whole Chromosome 18 Chromosome 18 Paint Red, green or blue 5 KBI-30018Whole Chromosome 19 Chromosome 19 Paint Red, green or blue 5 KBI-30019Whole Chromosome 20 Chromosome 20 Paint Red, green or blue 5 KBI-30020Whole Chromosome 21 Chromosome 21 Paint Red, green or blue 5 KBI-30021Whole Chromosome 22 Chromosome 22 Paint Red, green or blue 5 KBI-30022Whole Chromosome X Chromosome X Paint Red, green or blue 5 KBI-30023Whole Chromosome Y Chromosome Y Paint Red, green or blue 5 KBI-30024* Add -G for Green, -R for Red, -B for Blue (available on request)Whole Chromosome Probes87

Arm Specific ProbesArm Specific ProbesIn addition to our Whole Chromosome probes, wealso provide the entire series of Arm Specific Probes(ASP). These probes hybridize to unique sequencescomprising either p- or q-arms of all humanchromosomes (except the p-arm of the acrocentricchromosomes), and they span the entire length ofthe respective chromosome arm. They are derivedfrom flow-sorted or microdissected chromosomes,to be highly specific for each chromosome.Band Specific ProbesRearrangements affecting regions smaller thanan average G-band can be visualized using bandspecificFISH probes. These particular probes enhancethe resolution typically obtained with wholechromosome probes when identifying chromosomalabnormalities.ASP applications permit the detection of chromosomalaberrations at the resolution of chromosome arms. Thisallows the analysis of chromosome partners involved intranslocations, the identification of the chromosome of originof marker chromosomes, analyses of complex chromosomalrearrangements in neoplastic cells and studying the inbornsupernumerary marker chromosome as well as confirmationof results obtained from M-FISH and SKY testing. ASP maybe of particular interest to those studying mutagenesis ofhuman chromosomes, for instance as a result of exposureto genotoxic agents.Band-Specific probes are capable of detecting smallchromosomal segments, such as those involved in subtletranslocations with breakpoints localized in distinct bands.They are amplified from microdissected chromosomematerial and fluorescently labeled to allow detection of thesesubchromosomal regions. For an updated list of Band-Specificprobes please visit our website www.kreatech.comASP are developed for Research Use Only (RUO) andare not meant to be used for medical purposes or as adiagnostics tool. Our Arm Specific Probes are supplied ina ready-to-use format, and are available in two colors ofchoice: green and red.Arm Specific ProbesArm Specific Probes 2p and 6p showing a translocation ofchromosome 2p on chromosome 6p.Image kindly provided by Dr. Chantal Hamon, Paris.88

Ordering informationDescription Color Tests Cat#Arm Specific Probe 1p green or red 5 KBI-30100Arm Specific Probe 1q green or red 5 KBI-30101Arm Specific Probe 2p green or red 5 KBI-30102Arm Specific Probe 2q green or red 5 KBI-30103Arm Specific Probe 3p green or red 5 KBI-30104Arm Specific Probe 3q green or red 5 KBI-30105Arm Specific Probe 4p green or red 5 KBI-30106Arm Specific Probe 4q green or red 5 KBI-30107Arm Specific Probe 5p green or red 5 KBI-30108Arm Specific Probe 5q green or red 5 KBI-30109Arm Specific Probe 6p green or red 5 KBI-30110Arm Specific Probe 6q green or red 5 KBI-30111Arm Specific Probe 7p green or red 5 KBI-30112Arm Specific Probe 7q green or red 5 KBI-30113Arm Specific Probe 8p green or red 5 KBI-30114Arm Specific Probe 8q green or red 5 KBI-30115Arm Specific Probe 9p green or red 5 KBI-30116Arm Specific Probe 9q green or red 5 KBI-30117Arm Specific Probe 10p green or red 5 KBI-30118Arm Specific Probe 10q green or red 5 KBI-30119Arm Specific Probe 11p green or red 5 KBI-30120Arm Specific Probe 11q green or red 5 KBI-30121Arm Specific Probe 12p green or red 5 KBI-30122Arm Specific Probe 12q green or red 5 KBI-30123Arm Specific Probe 13q green or red 5 KBI-30124Arm Specific Probe 14q green or red 5 KBI-30125Arm Specific Probe 15q green or red 5 KBI-30126Arm Specific Probe 16p green or red 5 KBI-30127Arm Specific Probe 16q green or red 5 KBI-30128Arm Specific Probe 17p green or red 5 KBI-30129Arm Specific Probe 17q green or red 5 KBI-30130Arm Specific Probe 18p green or red 5 KBI-30131Arm Specific Probe 18q green or red 5 KBI-30132Arm Specific Probe 19p green or red 5 KBI-30133Arm Specific Probe 19q green or red 5 KBI-30134Arm Specific Probe 20p green or red 5 KBI-30135Arm Specific Probe 20q green or red 5 KBI-30136Arm Specific Probe 21q green or red 5 KBI-30137Arm Specific Probe 22q green or red 5 KBI-30138Arm Specific Probe Xp green or red 5 KBI-30139Arm Specific Probe Xq green or red 5 KBI-30140Arm Specific Probe Yq green or red 5 KBI-30141Band Specific Probes - inquire green or red 20 KBI-302xxArm Specific Probes*Add -G for Green, -R for Red89

Mouse FISH ProbesNew applications for mouse molecular cytogenetics are becoming apparent. Such applications include thedefinition of transgene integration sites in epigenetics studies, the characterization of the mouse genomeas a result of increasingly sophisticated techniques for its engineering and the screening for cytogeneticabnormalities in cell lines, such as embryonic stem cells. FISH mapping in mouse is complicated by the relativedifficulty of mouse chromosome identification (karyotyping) by laboratories that are not accustomed to mousechromosome banding techniques. Fluorescent karyotyping can be made easier by the use of counterstains ormultiple reference probes but each approach needs specialized equipment and experience.Cat.# KBI-30501 Cat.# KBI-30502 Cat.# KBI-30503Kreatech has developed a couple of mouse region-specificprobes prepared from defined BAC clones which are labeledwith PlatinumBright dyes.These mouse probes are commonly used when developingmodel systems for studies in the field of genetics, mutagenesis,developmental cancer biology and also as human surrogatesfor studying the effects of genotoxic agents.Ordering informationDescription Color Tests Cat#All Mouse Centromere (AMC) red/green 10 KBI-30500TK (11qE1) / AurKa (2qH3) red/green 10 KBI-30501TK (11qE1) / WC Y red/green 10 KBI-30502RAB9B (XqF1) / DSCR (16qC4) red/green 10 KBI-30503RAB9B (XqF1) / WC Y red/green 10 KBI-30505Mouse FISH Probes90Cat.# KBI-30500Hybridization of the All Mouse Centromere probe on mousemetaphase chromosomesFurther detailed information and the availability of theseprobes with other labels or other combinations are availableon request.

Customized DNA probesIn addition to the various FISH probes used for routine diagnostics and clinical research, an increasingnumber of FISH-based applications have emerged, such as reconfirming results obtained after array C G Hwith a cellular-FISH-based assay, and many more. These applications have raised the need for specific FISHprobes that currently are not commercially available. We at Kreatech are pleased to offer a customizedservice to our clients and researchers entering the field of FISH by providing probes custom-tailored forspecific projects or applications.The delivery time, initial order volume, and price for suchrequests will depend on complexity in design and access tothe DNA required to manufacture such a probe and will bedetermined on a case-by-case basis.In addition, we offer the possibility of obtaining an existingproduct from this catalog in another color, with anothercontrol probe, or anything else that may deviate from ourregular offering. Simply get in touch with us.The minimum requirement for such requests is an order of100 tests. Such service would include an upfront optimizationof the probe by Kreatech on your specific sample, and asubsequent validation of the customized probe in yourlaboratory prior to the full scale production.Please contact us to discuss your specific project and we willbe happy to assist you !Customized DNA Probes91

Chromogenic In Situ HybridizationChromogenic In Situ Hybridization (CISH) is increasingly emerging as a viable alternative to FISH and oftenselected as the method of choice for molecular pathologists for visualizing over-expression of genes involved intumor development. CISH, like FISH, directly visualizes the number of gene copies present in the nucleus, and itproduces a permanent record of the slide that can be interpreted with a regular light microscope in the contextof the tumor histopathology.TwinStarOur latest product range TwinStar is designed for dual-colorCISH enabling the possibility to study ratio of genes in alight microscope, like for the Her-2 gene in relation to thecentromeric region of chromosome 17. Each kit includesthe corresponding FISH probes and the specific TwinStardetection module converting both signals into chromogenicsignals via a colorimetric assay system.The TwinStar CISH Detection Kit is a module of all TwinStarassays including all reagents required to perform dual-colorCISH. The detection part includes two proprietary substratesconverting both fluorescent signals into distinct colorimetricsignals, the red fluor is converted into a red signal and thegreen fluor into a grayish-green signal. TwinStar provides auniversal solution capable of transforming all of Kreatech´sdual-color FISH probes into chromogenic signals.UniStarUniStar is based on a novel assay based on its well establishedPoseidon DNA probes, enabling the clinician to consecutivelyperform FISH and CISH on the same sample.In a first step, the sample is hybridized to specific fluorescentlabeledDNA probes enabling analysis under a fluorescencemicroscope. Subsequently, the fluorescent signal of the geneof interest can be converted into a chromogenic signal, whichcan then be analyzed with a regular bright field microscope.Alternatively, FISH can be omitted for direct CISH analysis.TissueSlide PretreatmentProbe HybridizationA. B.FISH AnalysisCISHCISHAmplified Her-2/Neu (ERBB2) on a breast cancer specimenvisualized with the TwinStar dual color CISH kit.Assay set-up for FISH and CISH analysiswith UniStarCISH92Each of the UniStar kits include the corresponding PoseidonDNA probes for copy number detection of the gene of interest,as well as a control probe for performing FISH in a dual-colorassay. In addition, they include a specific detection moduleconverting the signal of the critical probe into a chromogenicsingle-color signal via a colorimetric assay system.

Example of FISH and CISH performed consecutively on thesame slide: breast cancer tissue hybridized with the Her-2/Neu POSEIDON fluorescent probe followed by conversionof the red Her-2/Neu signal into a brownish chromogenicsignal using the UniStar CISH Detection Kit.Glioblastoma specimen showing amplified EGFR. Theslide was hybridized with the EGFR POSEIDON fluorescentprobe followed by conversion of the red EGFR signal into acolorimetric signal using the UniStar CISH Detection KitImage kindly provided by Dr. K. Beiske, Oslo University Hospital, NorwayProduct and ordering informationProduct Description Tests Cat#UniStar CISH Detection Kit UniStar CISH Detection Kit for the use with POSEIDON DNA Probes labeled in red 10 slides KBI-50001UniStar Her2/neu (17q12) DNA probes specific for Her-2/Neu and SE 17, UniStar CISH Detection Kit 10 Tests KBI-50701UniStar EGFR (7p11) DNA probes specific for EGFR and and SE 7, UniStar CISH Detection Kit 10 Tests KBI-50702UniStar C-MET (7q31) DNA probes specific for C-MET and and SE 7, UniStar CISH Detection Kit 10 Tests KBI-50719TwinStar CISH Detection Kit For the use with POSEIDON DNA probes labeled in red and green 10 slides KBI-60010TwinStar Her2/neu (17q12) DNA probes specific for Her-2/Neu and SE 17, TwinStar CISH Detection Kit 10 Tests KBI-60701TwinStar EGFR (7p11) DNA probes specific for EGFR and and SE 7, TwinStar CISH Detection Kit 10 Tests KBI-60702TwinStar C-MET (7q31) DNA probes specific for C-MET and and SE 7, TwinStar CISH Detection Kit 10 Tests KBI-60719CISH93

cell culture mediaKREAvital cytogenetic mediaOur product line KREAvital and related products have been carefully selected to optimally addresscytogenetic applications. They have been further optimized for best performance and undergo strict qualityprocedures ensuring consistent performance and superior results.KREAvital Prenatal Medium (Complete)The in vitro cultivation of amniotic fluid cells and chorionic villiis an essential part of every diagnostic cytogenetics laboratory,since the preparation of metaphase chromosome spreads isdependent upon obtaining cells in division. Amniocentesisand chorionic villi sampling are the major invasive diagnosticprocedures used for the detection of fetal chromosomalabnormalities. KREAvital Prenatal Medium is specificallyoptimized for the primary culture of human amniotic fluidcells and chorionic villi samples used in prenatal diagnostictesting. The medium is contains serum, glutamine andantibiotics, and greatly reduces karyotyping time comparedto conventional media.In addition to the complete ready-to-use medium, we alsoprovide KREAvital Prenatal as basal medium and supplementas separate components.Human AmniocytesCell Culture Media94KREAvital Prenatal Medium PLUS (Complete)Growing cells from amniotic fluids yield a mixture of epithelialcells, fibroblasts and amniocytes. KREAvital Prenatal MediumPLUS is an optimized formulation specifically enriching forfibroblasts and amniocytes, which are the cells best suitedfor genetic analysis. This circumstance ensures optimalchromosome morphology and metaphase structure formicroscopic observation, while reducing the relatively highbackground generated from having too much epithelialcells.KREAvital Prenatal Medium PLUS provides• Less epithelial cells• Clearer chromosome morphology for optimal bandinganalysis• Enhanced buffering capacity in closed systems• Prolonged stability when stored at 4°CKREAvital Lymphocyte Karyotyping MediumKREAvital Lymphocyte Karyotyping Medium is intended foruse in short-term cultivation of peripheral blood lymphocytesfor chromosome evaluation. It is based on RPMI-1640 basalmedium supplemented with L-Glutamine, fetal bovine serumand antibiotics. We provide this medium with and without theaddition of phytohaemagglutinin (PHA), respectively.

KREAvital Bone Marrow Karyotyping MediumAn increasing number of cytogenetic analyses are carriedout using bone marrow aspirates for studying chromosomalabnormalities in hematology.KREAvital Bone Marrow Karyotyping Medium is intended foruse in short-term cultivation of primary bone marrow cells forchromosome evaluation and has been optimized for providinga high mitotic index. It is based on RPMI-1640 basal mediumsupplemented with L-Glutamine, fetal bovine serum, andantibiotics. The medium does not contain any mitogens orconditioned medium.ColchicineColchicine is a secondary metabolite originally extracted fromplants of the genus Colchicum. In cell biology it is traditionallyused as a mitosis inhibitor to arrest cells in metaphase andallowing cell harvest and karyotyping to be performed.ColcemidColcemid, also known as demecolcine, is related to colchicine,but less toxic, and therefore increasingly popular as anequivalent mitosis inhibitor in cytogenetics.LymphocytesKREAvital Myeloid Cell MediumFresh cells or cells grown in short-term cultures often yield aninsufficient number of mitotic cells and repeated aspirationsare required. KREAvital Myeloid Cell Medium was developedto stimulate the proliferation of human hematopoietic cellsfrom bone marrow as well as peripheral blood. This medium isparticularly effective for karyotyping of acute non-lymphocyticleukemias and various stages of chronic myelogenousleukemia as well as other hematological disorders such asmyelodysplastic syndrome and polycythemia vera. KREAvitalMyeloid Cell Medium is based on MEM-Alpha basal mediumsupplemented with L-Glutamine, fetal bovine serum, antibioticsand conditioned medium.All KREAvital media include L-Glutamine and antibioticsTo secure rigorous quality assurance, each KREAvital batch is tested for cell growth in aleading clinical cytogenetics laboratory.Cell Culture Media95

PhytohaemagglutininPhytohaemagglutinin (PHA) is a lectin found in plants,especially beans. It has a number of physiological effectsand is used in medical research to trigger cell division inT-lymphocytes. In this function, PHA is the most commonlyused agent to induce mitosis in nondividing cells, such aslymphocytes and mature cells. Our PHA is provided asthe mucoprotein form (PHA-M). It is supplied sterile, in alyophilized form for constituting 5 ml of solution.Ordering informationDescription contents Cat#Cell Culture Media96KREAvital Prenatal Medium (Basal) 90ml KBI-90010KREAvital Prenatal Medium (Basal) 450ml KBI-92010KREAvital Prenatal Medium (Supplement) 10ml KBI-90011KREAvital Prenatal Medium (Supplement) 50ml KBI-92011KREAvital Prenatal Medium (Complete) 100ml KBI-90012KREAvital Prenatal Medium (Complete) 500ml KBI-92012KREAvital Prenatal Medium PLUS (Complete) 100ml KBI-90013KREAvital Prenatal Medium PLUS (Complete) 500ml KBI-92013KREAvital Lymphocyte Karyotyping Medium (without PHA) 100ml KBI-90020KREAvital Lymphocyte Karyotyping Medium (without PHA) 500ml KBI-92020KREAvital Lymphocyte Karyotyping Medium (including PHA) 100ml KBI-90021KREAvital Lymphocyte Karyotyping Medium (including PHA) 500ml KBI-92021KREAvital Bone Marrow Karyotyping Medium 100ml KBI-90030KREAvital Bone Marrow Karyotyping Medium 500ml KBI-92030KREAvital Myeloid Cell Medium 100ml KBI-90031KREAvital Myeloid Cell Medium 500ml KBI-92031AccessoriesColchicine Solution (10µg/ml, in PBS) 25ml KBI-90050Colcemid Solution (10µg/ml, in PBS) 10ml KBI-90051Potassium Chloride (0.075M) 100ml KBI-90052Phytohaemagglutinin M-Form 5ml KBI-90053Sodium Citrate Solution (0.8%) 500ml KBI-90054Trypsin EDTA 10X (EDTA 0.2%, Trypsin 0.5%, in saline solution) 20ml KBI-90055Trypsin EDTA 10X (EDTA 0.2%, Trypsin 0.5%, in saline solution) 100ml KBI-92055

EquipmentThermoBriteThis programmable system automates the denaturationand hybridization steps in slide-based in situ hybridizationprocedures, and provides walk-away convenience for clinicaland research personnel. The ThermoBrite accepts a wide rangeof sample types, is easy to use, and reduces hands-on time bymore than 50% while ensuring overall precision and accuracyin all FISH assays.CytoFuge ® 2The Cytofuge 2 is a low cost personal cytocentrifuge. It hassimply understandable controls and new snap-seal FilterConcentrators that make operation easy. Samples are processedquickly, silently, and conveniently on any bench or in a safetycabinet. Results are consistent: easy to scan monolayer cellpresentations of excellent morphologic detail.ThermobriteSlide DenaturationHybridization SystemThe CytoFuge 2is ideal for a completerange of body fluids:• Pleural fluids• Sputum• Urine• Synovial fluids• Fine needle aspirates• Bronchial washings• Cerebrospinal fluidsThe ThermoBrite accommodates up to 12 slides and maintainsuniform temperature across all slide positions. The lid sealstightly when closed providing optimal chamber humidity. Thenumeric keypad allows for easy programming with 40 userprogrammable settings and 3 modes of operation; denaturation/hybridization, hybridization, and fixed temperature.ThermoBrite and CytoFuge 2 are trademarks of StatSpin, a division of IRIS SampleProcessingSpecificationsSafety features:Rotor capacity:Cover interlock systemLeak-resistant rotor with transparent lidLow voltage drive system (24V)Designed to meet requirements of IEC-1010-2-020One to four slidesSpeed: 600 RPM (20 x g) 1300 RPM (93 x g)700 RPM (27x g) 1600 RPM (140 x g)850 RPM (40 x g) 2200 RPM (265 x g)1000 RPM (55 x g) 4400 RPM (1060 x g)Dimensions:15,2 cm x 16,8 cm x 21,8 cmWeight:2,5 kgOrdering informationDescriptionCat#ThermoBrite (120V, 50-60Hz)TS-01ThermoBrite (240V, 50-60Hz)TS-02Humidity Control Cards 10 HC-10Cytofuge2 (100 - 240V, 50 / 60 Hz)*CF-02Reusable Filter Concentrators 20 FFR1Filter Concentrators (disposable) 192 FF01-B*) not available in all countries. Please inquireEquipment97

Kits and ReagentsThe ready-to-use pretreatment kits are recommended to be used with Poseidon FISH DNA probes to producehigh quality results. The kits contain all necessary ready-to-use reagents used for slide pretreatment andwashing steps for FISH. The reagents increase the permeabilization of the cell membranes to facilitatepenetration of the Poseidon FISH DNA probes. The pretreatment kits will allow to process up to 25 slides inbatches of 5 slides per experiment.The selection table can guide you which pretreatment kit isthe most optimal for your sample type:SampleKBI-60005 KBI-60006 KBI-60007 KBI-60004Freshly prepared cytological samples + (+)Pretreatment KitsTissue Digestion Kit I (KBI-60007)Tissue Digestion Kit I contains all necessary ready-to-usereagents to be used for pretreatment of conventionalparaffin-embedded tissues.Older / difficult samples (+) +Standard tissue + (+)Heavily cross-linked tissue (+) +Tissue Digestion Kit II (KBI-60004)Tissue Digestion Kit II contains all necessary ready-to-usereagents to be used for pretreatment of heavily cross-linkedparaffin-embedded tissue. The Tissue Digestion Kit II providesa more intense pretreatment for optimal performance.FISH Reagent Kit (KBI-60005)FISH Reagent Kit contains all necessary ready-to-usereagents to be used for basic pretreatment of freshlyprepared cytological samples.Kits and ReagentsFISH Digestion Kit (KBI-60006)FISH Digestion Kit consists of ready-to-use reagents designed toobtain optimal results with older/difficult cytological samples orsamples with cytoplasmic background which have been fixed inalcohol based fixatives (e.g. Carnoy’s). Reagents provided allowto perform mild digestion on difficult cytogenetic samples,such as uncultured amniocytes, direct blood smears, buccalscrapings, urine, touch preps and others.98

ReagentsFISH Hybridization BufferFISH Hybridization Buffer (FHB) is a ready -to-use hybridizationsolution used for Poseidon FISH DNA probes. FHB containsformamide, SSC, and Dextran Sulfate. Qualified for use forstandard cytological and all kind of direct samples (unculturedamniocytes, blood, bone marrow, buccal scrapin, urine etc.).FHB is provided with all Poseidon Satellite Enumeration andSub-Telomeric probes.Paraffin Tissue BufferParaffin Tissue Buffer (PTB) is a ready-to-use hybridizationsolution for Poseidon FISH DNA probes. PTB containsformamide, SSC, and Dextran Sulfate. Qualified for use onParaffin tissues.Whole Chromosome BufferWhole Chromosome Buffer (WCB) is a ready- to- usehybridization solution for Poseidon Whole Chromosomeprobes. WCB contains formamide, SSC, and Dextran Sulfate.Qualified for use on standard cytological samples. WCB isprovided with all Poseidon Whole Chromosome probes.Rubber Cement, FixogumFor use in the formation of an air tight seal around theperimeter of the glass coverslip during probe hybridizationfor FISH.Ordering informationDescription Contents Cat#POSEIDON Tissue Digestion Kit II 5x5 slides KBI-60004POSEIDON FISH Reagent Kit 5x5 slides KBI-60005POSEIDON FISH Digestion Kit 5x5 slides KBI-60006POSEIDON Tissue Digestion Kit I 5x5 slides KBI-60007Igepal 5 ml LK-069ARubber Cement, Fixogum 125 ml LK-071ADAPI Counterstain (0.1µg/ml) 500 µl LK-095BDAPI Counterstain (1µg/ml) 500 µl LK-096BCounterstain Diluent 500 µl LK-097BFISH Hybridization Buffer (FHB) 100 µl KBI-FHBParaffin Tissue Buffer (PTB) 100 µl KBI-PTBWhole Chromosome Buffer (WCB) 50 µl KBI-WCBKits and Reagents99

FISHBright labeling kitsThe FISHBright labeling kits are based on KREATECH’s Universal Linkage System (ULS). The ULS moleculeis a proprietary platinum compound linked to a hapten or a fluorophore. The FISHBright kits offer ULSmolecules coupled to a variety of fluorophores or haptens providing a non-enzymatic, easy-to-use alternativeto conventional techniques such as nick translation, random priming, end labeling, etc.The FISHBright labeling kits are specially developed for FISH applications: labeled DNA probes can be usedon all type of samples including metaphase spreads, direct interphase cell preparation (e.g. blood smears,bone marrow smears), urine samples, paraffin-embedded or frozen tissue sections.KREATECH’s Poseidon probes are labeled with the same technology and all Poseidon pretreatment kits can beused in combination with DNA probes which are labeled with the FISHBright labeling kits.Besides the ULS technology the kits also contain Cell specific Hybridization Buffer (CHB), and TissueHybridization Buffer (THB). In addition, the KREAboost solution, which is developed to generate a high signalto-noiseratio especially on paraffin-embedded tissue sections, is included in these kits.The FISHBright labeling kits will offer you alladvantages of the ULS technology:• Simple to use• Labeling procedure within 30 minutes• Use of KREApure columns: a unique purification columnwhich guarantees a very high removal of non reacted ULS(> 99%) and high sample recoveries (> 95%).FISHBright labeling kitsContent:• PlatinumBright component (fluorochromes or haptens)• 10 x labeling solution• KREApure purification columns• Hybridization buffer for cytological preps (CHB)• Hybridization buffer for paraffin preps (THB+KREAboost)FISHBright Labeling KitsOrdering informationThe FISHBright kit contains sufficient solution to label up to10 μg of BAC DNA, which generally allows to perform 100 ormore FISH assays using 10 μl labeled probe in hybridizationbuffer (amount of FISH assays is dependent on the finalconcentration of labeled DNA. Usually 50 – 100 ng/μl of labeledBAC DNA is necessary per assay).Description Contents Cat#FISHBright 415 Blue for labeling 10 µg DNA FLK-001FISHBright 495 Green for labeling 10 µg DNA FLK-002FISHBright 505 Green for labeling 10 µg DNA FLK-003FISHBright 550 Red for labeling 10 µg DNA FLK-004FISHBright 547 Light Red for labeling 10 µg DNA FLK-005FISHBright 647 Far Red for labeling 10 µg DNA FLK-006FISHBright Biotin for labeling 10 µg DNA FLK-007100FISH Grade CoT 500 µg KB-COT

FISHgrade CotFISHgrade C 0 t DNA is extracted from human placental DNAtreated under conditions that enrich for repetitive DNAsequences (1,2). These conditions have been optimized byKreatech Diagnostics for the specific use in FISH experiments.FISHgrade C 0 t DNA suppresses cross-hybridization to humanrepetitive DNA. Amounts of FISHgrade C 0 t DNA needed in aFISH experiment should be determined empirically, but willbe in the order of 12.5 – 50 times excess to the amount oflabeled genomic DNA.• High quality human C 0 t-1 DNA optimized for use in FISHapplication• Specific quality control with FISH analysis• Works perfectly for probes labeled with FISHBright ULS-Kits.Cat.# KB-COT FISHgrade CotFISH image on metaphase spread performed using a classical FISHprobe labeled in red/green colors using a FISHBright labelingkit. FISHgrade C0t DNA has been used to block all aspecific DNAsequences. The probe specifically recognizes deletions at 20qchromosome that have been related to myelodysplastic syndromes.References1. Weiner, A.M., et al. (1986) Ann. Rev. Biochem. 55, 631.2. Britten, R.J., et al. (1974) Methods Enzymol. 29, 363.Ordering informationCat#FISHgrade Cot 500 μg KB-COTFISHBright Labeling Kits101

Product Selection GuideULSArray CGHULS array CGH Labeling Kit104cDNAULS cDNA Synthesis and Labeling Kit104Gene ExpressionLabelingULS aRNA Labeling Kits106aRNAAmplification& LabelingRNA ampULSe Kits106MicroarrayLabelingmiRNA detectionULS microRNA Labeling Kit107Protein arraysULS Protein Labeling Kits108General NucleicAcid LabelingPlatinumBright Kits109Product Selection GuideAntibodyLabelingPlatinumLink Kits110102

THE ULS LABELING TECHNOLOGYIntroductionONE LABELING Technology for all Microarray and FISH applicationsThe proprietary ULS (Universal Linkage System) technology provides the basis for KREATECH’s broad rangeof labeling applications. ULS labeling is based on the stable coordinative binding properties of platinum tonucleic acids and proteins. The ULS molecule consists of a platinum complex, a detectable molecule and aleaving group which is displaced upon reaction with the target. This reaction results in a coordinative bond,firmly coupling the ULS to the target. ULS labels DNA and RNA by binding to the N7 position of guanine. Inproteins, ULS binds to sulfur and nitrogen containing side chains of methionine, cysteine and histidine. ULS isavailable coupled to a variety of labels and haptens, including fluorochromes and biotin. The labeling reactionallows a wide range of conditions and produces a highly stable bond.Principle of the ULS technologyTargets labeled with ULSNucleic AcidsGuanineULS labels DNA andRNA by forming acoordinative bondon the N7 positionof guanineProteinsMethionine, Cysteine, HistidineULS labels proteins by forminga coordinative bond on thesulfur atoms of methionine,cysteine and the nitrogen atomof histidineUnique features of the ULS Labeling Technology• Time saving: Entire labeling procedure in only 30 minutesfor DNA and 15 minutes for RNA• Easy to use• Robust and reproducible – no enzymes involved• Superior labeling technology for FFPE samples• One technology for all applications• Compatible with all microarray platformsThe ULS Labeling Technology103

DNA LABELINGULS arrayCGH Labeling KitThe ULS arrayCGH Labeling Kit offers a novel procedurethat allows direct (non-enzymatic) labeling of both intactgenomic DNA as well as fragmented genomic DNA isolatedfrom formalin-fixed paraffin-embedded (FFPE) samples.The ULS arrayCGH Labeling Kit yields highly reproduciblefluorescent labeled DNA within minutes. The ULS technologyhas been validated on a wide range of array CGH platforms.All ULS kits for array CGH analysis include the KREApurepurification technology and KREAblock blocking reagents toensure efficient purification of labeled DNA samples and lowbackground levels during hybridization.ULS cDNA Synthesis and Labeling KitThe ULS cDNA Synthesis and Labeling Kit provides the optionto generate unmodified cDNA followed by direct labeling withthe ULS technology. These kits are superior to other enzymaticprotocols by allowing the use of natural nucleotides, thereforeresulting in better efficiency of the reverse transcriptase andreducing the chance of bias. The ULS cDNA Synthesis andLabeling Kits include all reagents for reverse transcription andsubsequent cDNA labeling.Unique features of ULS arrayCGH Labeling Kit• 30 minutes labeling procedure• Labeling independent of fragment size - ideal for FFPEsamples• ULS labeling is not affected by cross links present ingenomic DNA from FFPE samples• No enzymatic bias• KREApure column purification ideally suited forfragmented DNAUnique Features of the ULS cDNA Synthesisand Labeling Kit• Generation of cDNA with unmodified nucleotides to allowmost efficient transcription• Unmodified cDNA can be used for other assays• Labeling efficiency independent of fragment lengthULS Labeling vs Random Prime LabelingTime of ULS labeling vs. enzymatic labeling procedureA B triplo CcorrelationULScoefficientLabeling = 0.96ULSCompetitor Alabelingclean upD E triplo FDNA LabelingRandomcorrelationPrimecoefficientLabeling = 0.88Ratio plots of 3 independent array CGH hybridizations using genomic DNA from healthyliver which is the reference vs. genomic DNA isolated from a liver tumor FFPE sample.(A-C) ULS labeled samples. (D-F) Random Prime labeled samples.Competitor B0 h0,5 h1 h1,5 h2 h2,5 h3 h3,5 h4 h16 h104

Array-Grade KREAcot DNAArray-Grade KREAcot DNA is extracted from human placentalDNA and subsequently fragmented, denatured, and re-annealedunder conditions that enrich for repetitive DNA sequences(1,2). Array-Grade KREAcot DNA can be used to suppresscross-hybridization to human repetitive DNA sequences. Array-Grade KREAcot DNA has specifically been optimized to be usedin array CGH applications. Amounts of Array-Grade KREAcotDNA needed in a microarray experiment should be determinedempirically, but will be in the order of 12.5-50 times excess tothe amount of labeled genomic DNA. Please visit the Kreatechwebsite (www.kreatech.com) for a detailed protocol for theanalysis of genomic DNA using array CGH.Megapool Reference DNAThis product is a homogeneous DNA pool from male orfemale human genomic DNA which has been isolated from100 different anonymous healthy individuals. The genomicDNA is of high quality and the DNA from each of these 100individuals contributes evenly to the DNA pool. This product isspecifically developed as a reference for genomic microarraybasedcomparative genomic hybridization experiments (arrayCGH).Unique features of Array-Grade KREAcot• Specifically optimized for use in array CGH applications• Quality controlled with array CGH analysisUnique features of the MegaPool Reference DNA• The product will guarantee perfectly comparable profiles formale and female individuals as well as complete absence ofpure homozygous deletions.• Sex-matched array CGH experiments will be possible andenable high-quality genotyping data for both chromosomesX and Y as well as unbiased CNV profiles between male andfemale test samples.Comparison of performance of Array-Grade KREAcot DNA andhuman C0t-1 DNA from competitor X.Ordering informationDescription Contents Cat#Array-Grade KREAcot2 log ratio for X chromosome = -0.65Mean absolute deviation forchrom 1-22 = 0.05Human C 0 t-1 DNA competitor X2 log ratio for X chromosome = -0.66Mean absolute deviation forchrom 1-22 = 0.11Shown are the chromosome plots obtained from an array CGH hybridization comparinghealthy male Cy5-ULS labeled genomic DNA and healthy female Cy3-ULS labeledgenomic DNA on BAC microarrays. Although the spread observed for the X-chromosomeis comparable for both blockers, the use of Array-Grade KREAcot minimizes the variationobserved for chromosomes 1-22.ULS cDNA synthesis and Labeling 10 dual labeling reactionsDSK-001Kit (with Cy3 and Cy5)(2 x 50 µg cDNA)ULS cDNA synthesis and Labeling 20 single labelingKit (with Cy5)reactions (100 µg cDNA)DSK-002ULS cDNA synthesis and Labeling 20 single labelingKit (with Cy3)reactions (100 µg cDNA)DSK-003ULS cDNA synthesis and Labeling 20 single labelingKit (with Biotin)reactions (100 µg cDNA)DSK-004ULS arrayCGH Labeling Kit for labeling 2 x 20 µg(with Cy3 and Cy5)DNAEA-005ULS arrayCGH Labeling Kit(with Cy3)for labeling 40 µg DNA EA-005AULS arrayCGH Labeling Kit(with Cy5)for labeling 40 µg DNA EA-005BArray-Grade KREAcot DNA 500 μg EA-020Array-Grade KREAcot DNA 10 mg EA-035Megapool Reference DNA (male) 200 µg EA-100MMegapool Reference DNA (female) 200 µg EA-100FDNA Labeling105

RNA LABELINGAMPLIFICATION AND aRNA LABELING KITSaRNA Labeling KitsThe Universal Linkage System (ULS) allows direct labeling ofunmodified, amplified RNA (aRNA). Specific aRNA labeling kitsare both available for the use with commercial platforms fromAgilent, Affymetrix ® (Genechips ® ) and CombiMatrix, and forthe use with self-spotted DNA arrays.RNA ampULSe KitsThe RNA ampULSe kit combines two successful technologies.The aRNA is generated with Ambion’s MessageAmp II aRNAamplification reagents followed by non-enzymatic labelingwith KREATECH’s proprietary Universal Linkage System (ULS)technology. Specific ampULSe kits are both available for theuse with commercial platforms from Agilent, Affymetrix ®(Genechips ® ) and CombiMatrix, and for the use with selfspottedDNA arraysUnique features of aRNA Labeling Kits• Higher yields of unmodified aRNA compared to modifiedaRNA• Storage of unmodified aRNA for subsequent use possible• No waste of labeled material; label only the amount aRNAneeded• Reduced labeling cost per hybridization when usingmultiple arrays per slideHigher yields of unmodified aRNA as compared to modified aRNALower cost if multiple arrays per slide are used160unmodified aRNAmodified aRNA100ULS labelingEnzymatic labelingaRNA yield (µg)140120100806040200HeLa U2OS JurkatHuman samples (starting with 5 µg total RNA)Relative costs per sample(compared to 1 array/slide)90807060504030201001 2 4 8 12Number of arrays on 1 slideRNA LabelingUnmodified antisense RNA (aRNA) vs. modified aRNACosts for ULS labeling of unmodified aRNA vs. costs for enzymatic labelinggenerating modified aRNA106

microRNA Labeling KitThe new ULS microRNA Labeling Kit provides a very simple andfast method for miRNA detection on microarray platforms. TheUniversal Linkage System (ULS) labeling technology is used todirectly label the naturally occurring miRNAs which are present inthe total RNA mixture without the need to enrich for small RNA.ULS can be used to label total RNA from all kind of organisms.Unique features of the ULS microRNA Labeling Kit• 15 minutes labeling step• Easy two-step procedure to label total RNA• Compatible with most existing miRNA platforms• Not size discriminativeTime of ULS labeling vs. competitive labeling technologies.ULSlabelingclean up1412Competitor ACompetitor B0 h0,5 h1 h1,5 h2 h2,5 h3 h3,5 h4 h6,5hMedian Cy3 (logBGC)1086correlation coefficient= 0.996 8 10 12 14Median Cy5 (logBGC)Ordering informationDescription Contents Cat#RNA LabelingULS microRNA Labeling Kit (with Cy3 and Cy5) for labeling 2 x 25 µg RNA EA-036ULS microRNA Labeling Kit (with Cy3) for labeling 50 µg RNA EA-037ULS microRNA Labeling Kit (with Cy5) for labeling 50 µg RNA EA-038ULS aRNA Labeling Kit (with Cy3 and Cy5) for labeling 2 x 50 µg aRNA EA-006ULS aRNA Labeling Kit (with Biotin for Affymetrix® Genechips®) for labeling 500 µg aRNA EA-010ULS aRNA Labeling Kit (with Biotin) for labeling 250 µg aRNA EA-018ULS Fluorescent Labeling Kit for Agilent arrays (with Cy3 and Cy5) for labeling 2 x 50 µg aRNA EA-021ULS Fluorescent Labeling Kit for Agilent arrays (with Cy5) for labeling 50 µg aRNA EA-022ULS Fluorescent Labeling Kit for Agilent arrays (with Cy3) for labeling 50 µg aRNA EA-023ULS Labeling Kit for CombiMatrix arrays (with Cy5) for labeling 125 µg aRNA EA-025ULS Labeling Kit for CombiMatrix arrays (with Biotin) for labeling 125 µg aRNA EA-027RNA Amplification and Labeling (20 amplifications each)RNA ampULSe Amplification and Labeling Kit (with Cy3 and Cy5) for labeling 2 x 20 µg aRNA GEA-001RNA ampULSe Amplification and Labeling Kit (with Biotin for Affymetrix® Genechips®) for labeling 40 µg aRNA GEA-004RNA ampULSe Amplification and Labeling Kit (with Biotin) for labeling 200 µg aRNA GEA-006RNA ampULSe Amplification and Labeling Kit (with Cy3 and Cy5 for Agilent arrays) for labeling 2 x 20 µg aRNA GEA-014RNA ampULSe Amplification and Labeling Kit (with Cy5 for Agilent arrays) for labeling 40 µg aRNA GEA-016RNA ampULSe Amplification and Labeling Kit (with Cy3 for Agilent arrays) for labeling 40 µg aRNA GEA-018RNA ampULSe Amplification and Labeling Kit (with Cy5 for CombiMatrix arrays) for labeling 100 µg aRNA GEA-022RNA ampULSe Amplification and Labeling Kit (with Biotin for CombiMatrix arrays) for labeling 100 µg aRNA GEA-026All RNA ampULSe Kits include Ambion’s MessageAmp II aRNA amplification reagents and the ULS-based labeling moduleRNA Labeling107

PROTEIN LABELINGPROTEIN LABELING AND DETECTION KITS FOR ANTIBODY ARRAYSThe ULS Protein Labeling and Detection Kits are based on KREATECH’s Universal Linkage System (ULS). The kitsprovide an easy and reproducible method for labeling proteins from serum, plasma and cell lysates, as well asdetection of analytes on antibody arrays. Kits are available in dual color format and are compatible with manyarray surfaces and commercial array platforms. For single color kits, please inquire.Unique features of the Protein Labeling andDetection Kits• All reagents provided in one kit.• Compatible with most salts, buffers and detergents• ULS-Trap purification columns - removes all unreactedULS label• Provides high coverage (>98%) of the proteome throughspecific labeling of methione, cysteine, and histidine residuesDual color Cell lysate incubated on Clontech antibody array slide.Dual color Serum incubated on nitrocellulose-based antibody array.Protein LabelingOrdering informationDescription Reactions Cat#Two-color ULS Serum and Plasma Protein Labeling and Detection Kit 4 dual labelings PLK-001Two-color ULS Cell Lysate Protein Labeling and Detection Kit 4 dual labelings PLK-002108

GENERAL NUCLEIC ACID LABELINGPLATINUMBright Labeling KitsThe PlatinumBright Nucleic Acid Labeling Kits are based onKREATECH’s patented Universal Linkage System (ULS). TheULS molecule is a proprietary platinum compound linked toa hapten or a fluorophore. The PlatinumBright kits offer ULScoupled to a variety of fluorophores or biotin providing a nonenzymatic, easy to use alternative to conventional techniquessuch as nick translation, random priming, end labeling, etc.Unique features of the PlatinumBrightLabeling Kits• Only a two-step very fast labeling procedure• Easy to perform• A variety of labels to choose from• Not dependent on the performance of enzymesThe labeled nucleic acid can be used for the downstreamapplication of your choice. In addition to the PlatinumBrightNucleic Acid Labeling Kits KREATECH also offers the FISHBrightkits which, in addition to reagents for labeling, include allreagents needed for FISH hybridization (see page 79).Centromere 11 labeled with PlatinumBright 415.4-color FISH.Ordering informationDescription Reactions Cat#PlatinumBright Nucleic Acid Labeling Kit (495 Green) for labeling 20 µg template GLK-001PlatinumBright Nucleic Acid Labeling Kit (547 Light Red) for labeling 20 µg template GLK-002PlatinumBright Nucleic Acid Labeling Kit (647 Far Red) for labeling 20 µg template GLK-003PlatinumBright Nucleic Acid Labeling Kit (550 Red) for labeling 20 µg template GLK-004PlatinumBright Nucleic Acid Labeling Kit (570 Red) for labeling 20 µg template GLK-005PlatinumBright Nucleic Acid Labeling Kit (415 Blue) for labeling 20 µg template GLK-006PlatinumBright Nucleic Acid Labeling Kit (Biotin) for labeling 20 µg template GLK-007General Nucleic Acid Labeling109

Antibody LABELINGPlatinumLink Antibody Labeling KitsThe PlatinumLink Kits provide high coverage of theproteome through specific labeling of methionine, cysteineand histidine residues. Unlike lysine, which is targeted byN-hydroxysuccinimidyl (NHS) esters, the amino acids labeledwith ULS are less likely to be involved in protein - proteininteractions. Therefore, labeling of proteins and antibodieswith ULS will reduce negative effects on interaction domainsand epitope recognition.The PlatinumLink Antibody Labeling Kits have been optimizedto label 100 μg of purified antibody (or recombinant protein)per reaction with fluorescent dyes or haptens.Unique features of the PlatinumLink AntibodyLabeling Kits• Easy and robust labeling of antibodies and recombinantproteins• ULS-Trap removes unreacted label, no size exclusion• Labeling of methionines, cysteines and histidines inantibodies and recombinant proteins• Labeling reaction is independent of pH• Compatible with commonly used detergents includingTris-HClSchematic overview of the PlatinumLink labeling procedure.Recovery comparison of different proteins.Step 1: Protein labelingStep 2: Removal of unreacted ULS-label100100 µg proteinULS-label labeling buffer908070o/n 37°Clabeled sampleapply to ULS-Trap columncentrifuge 1 min60504030purified labeledprotein sample% recovery20100catalasebovinealbuminconalbumin anti-humanIgGanti-humanIgGanti-mouseIgGAntibody Labeling110Ordering informationFig.18 Protein recovery using ULS-Trap columns 100 µg of protein was labeled and purified using PlatinumLink protein labeling kits. Protein concentration was determined usingBiorad’s Rc Dc protein assay. Recovery is presented as percentage protein recovered ascompared to unpurified sample.Description Reactions Cat#PlatinumLink Protein Labeling Kit (BIO) 4 single labelings PLK-007PlatinumLink Protein Labeling Kit (FLU) 4 single labelings PLK-009PlatinumLink Protein Labeling Kit (RHO) 4 single labelings PLK-010

KREApureKREApure purification columns and platesKREApure purification columns and plates are based on a proprietarypurification matrix optimized for purifying ULS-labeled targetnucleic acids. The procedure quantitatively removes non-attachedlabel and provides optimal recovery of labeled nucleic acids.Unique features of the KREApure purification• Maximal removal of unreacted ULS-label• > 95% recovery of labeled nucleic acid• Efficient recovery of small fragmentsKREApure spin column purification.KREApure 96-well procedure.ReactionmixtureWash the column materialSpin for1 minuteUnreactedULSAdd ULS labeled materialSpin for1 minuteKREA purespin columnCollectiontubeSpin 1 minuteMax. speedBenchtop centrifugePurified,labeled targetCollect purified labeled materialYield comparison of different purification methods.100Cy3 ULS yields vs not purified7550Yields in %250KREApure Precipitation Silica column Gelfitration Size exclusionCy3 – ULS-labeled DNA has been purified using five different purification systems.Experiments were performed in triplicate.Ordering informationDescription Reactions Cat#KREApure columns 20 pcs KP-020KREApure columns 50 pcs KP-050KREApure 96* 1 plate KP-096* specific high-throughput labeling modules available upon requestKREApure111

Technical AppendixThe Poseidon Probe MapsAll locus specific probes are provided with a map showingthe genome region and/or genes the probe will cover. The STSmarkers indicating the most proximal and distal end coveredby the probe are added as well. Those markers can be used todescribe in situ hybridization results in accordance with theInternational System for Human Cytogenetic Nomenclature(ISCN, 2009). For more information see e.g. Genome Browserat genome.ucsc.edu or Ensemble at www.ensembl.orgRB1Most proximal marker covered by probeD13S147713q14 RFP2DLEU1D13S272650 KB220 KBTarget Gene (or Genes) covered by ProbeProbe size and color indication13D13S25450 KBProbe maps not to scaleMost distal marker covered by probeDistance to another region or gene of interestKreatech’s fluorophores and filter recommendationsStandard fluorophores used forPoseidon FISH probesFluorophore Color Excitation/EmissionPlatinumBright415 Blue 429/470PlatinumBright495 Green 495/517PlatinumBright550 Red 550/580Fluorophores used in PlatinumBright andFISHBright Labeling KitsFluorophore Color Excitation/EmissionPlatinumBright415 Blue 429/470PlatinumBright495 Green 495/517PlatinumBright505 Green 500/528PlatinumBright550 Red 550/580Technical Appendix112Fluorophores used in PGS kits(KBI-40050; 40051; 40060-40064)Fluorophore Color Excitation/EmissionPlatinumBright405 Dark Blue 410/455PlatinumBright415 Blue 429/470PlatinumBright495 Green 495/517PlatinumBright547 Light Red 547/565PlatinumBright590 Dark Red 587/612PlatinumBright647 Far Red 647/665PlatinumBright547 Light Red 547/565PlatinumBright570 Dark Red 570/591PlatinumBright647 Far Red 647/665When ordering a filter from Chroma or other suppliers pleasemake sure to either have a cube or slider available for yourspecific brand and type of microscope.Filters from other suppliers covering the same excitation andemission wavelengths as described above will also workperfectly with Poseidon probes. For further questions pleasecontact customerservice@kreatech.com

Recommended Filters:Single FiltersFluorophore Ex/Em Color Recommended Filter Excitation Filter Dichromatic Mirror Emission Filter Filter (Chroma cat#)DAPI DAPI DAPI / UV 360/20 400 LP 425 LP 11000PlatinumBright405 410/455 Dark Blue Blue 405/10 425 LP 460/50 31016 / 31037 / 31047PlatinumBright415 429/470 Blue Aqua 436/20 455 LP 480/30 31036v2PlatinumBright495 495/517 Green FITC / Green 480/30 505 LP 535/40 31001 / 41001PlatinumBright505 500/528 Green FITC / Green 480/30 505 LP 535/40 31001 / 41001PlatinumBright550 550/580 Red TRITC 540/25 565 LP 605/55 31002 / 41002PlatinumBright547 547/565 Light Red Cy3 / Gold 535/50 565 LP 610/75 31002 / 41002PlatinumBright570 570/591 Red Texas Red 560/40 595 LP 645/75 31004 / 41004PlatinumBright590 587/612 Dark Red Texas Red 560/40 595 LP 645/75 31004 / 41004PlatinumBright647 647/665 Far Red Cy5 / Far red 620/60 660 LP 700/75 41008Dual/Triple FiltersFluorophore Color Recommended Filter Excitation Filter Dichromatic Mirror Emission Filter Filter (Chroma cat#)PlatinumBright495/550 Green/Red Dual FITC/Cy3PlatinumBright 415/495/550 Blue/Green/Red DAPI/FITC/Cy3DAPI / PlatinumBright 495/550DAPI/Green/RedDAPI/FITC/TRITC or Cy3485/10563/12430/12490/12562/12396/8482/8554/14500-550580 LP446-478503-548579 LP440-472498-540573 LP521/20595 LP463/10523/15585 LP450/10516/20604/22510096101061000v2Optimal template amount for using Kreatech’s ULS labeling kits250 ngAPPLICATIONS2 µgTARGETarrayCGHGenomic DNA20 µgGeneExpressionmicroRNA1 µg1 µg5 µg10 µg10 µgaRNAtotalRNAtotalRNA100 µg DNA/RNATechnical Appendix113

TERMS AND CONDITIONSTerms and ConditionsKREATECH warrants that, at the time of shipment, theproducts sold are free from defects in materials and conformto the specifications described in KREATECH’s literature.KREATECH makes no other warranty, expressed or implied,with respect to the products. This includes any warranty ofmerchantability or suitability for any particular purpose.KREATECH’s Poseidon FISH products are supplied for invitro Diagnostics (or for research use only if not CE marked).They are not intended to be used as drugs, food, additives,cosmetics or household chemicals.Terms and Condition of SalePayments are net 30 days from the date shown on the invoice.Prices are subject to change without notice. All orders under€ 400,- will be charged with the shipping costs.Methods of payment including Credit CardordersWhen placing an order via fax or over the telephone withone of our Sales and/or Customer Service representatives,KREATECH requires that all customers provide a purchaseorder number. To better serve your needs, KREATECH acceptsMasterCard and VISA as payment for orders. Please providecredit card type, name of the card holder, credit card number,expiration date and security code when placing credit cardorders.Shipping PolicyOrders for regularly stocked items received by 14:00 CETMonday through Thursday are shipped the same day. Ordersreceived after 14:00 are shipped the following day. Ourminimum guaranteed shelf life is 6 months upon shipment.In the event that an order contains a non-stocked item, orif, for any reason, KREATECH is unable to completely fulfillan order, a partial shipment will be made unless instructedotherwise. You will be notified immediately of any delay.THE KREATECH Customer Satisfaction PolicyIf you are not completely satisfied with the performance ofany product, KREATECH will, at your option, either credit youraccount or send a replacement product to you at our expense.Requirements for this are that the product has not expired,it has been stored and processed according to KREATECHproduct literature and that the user followed all appropriateKREATECH protocols when using the product.Returned Goods PolicyReturned goods will not be accepted without the priorauthorization of KREATECH. Unauthorized returns will bereturned at the sender’s expense. Complete documentationmust accompany all authorized returned goods. If shippingerrors are made by KREATECH leading to loss of goods,KREATECH will replace goods at KREATECH´s expense.Product UseAll products manufactured and/or distributed by KREATECHshould be used in accordance with the products labelledintended use of the given product.PatentsThese products or the use of these products is subject toproprietary rights. FISH probes are labelled with the UniversalLinkage System (ULS). The fluorophores used in thePlatinumBright-415, -547, -590, -647 labelling compound issubject to patents, owned or controlled, and manufactured byDYOMICS GmbH. The fluorophores used in ULS-Cy5 labelingcompounds are subject to patents, owned or controlled, andmanufactured by GE Healthcare. The ULS technology andproducts are covered by US patents 5,580,990; 5,714,327;5,985,566; 6,133,038; 6,797,818 and several foreign patentsowned by KREATECH. KREATECH is a trade name of KREATECHBiotechnology B.V., ULS , PlatinumBright, KreaPure,KreaBlock and Poseidon are trademarks of KREATECHBiotechnology B.V.Nothing disclosed herein is to be construed as a recommendationto use any of KREATECH products in violation of any patents.Furthermore, KREATECH does not warrant that the product,either alone, or in combination with other products, is immunefrom charges of patent infringement. KREATECH will not beheld responsible for patent infringements or other violationsthat may occur from the use of any of its products.114

CE Marking & ISO certificatesAll probes from Kreatech are manufactured and marketed inaccordance with the European IVD Directive 98/79/EC. Apartfrom those products designed for research use (Kreatech´sASP, BSP, and mouse FISH probes, as well as the ULS Labelingproduct line), all Kreatech products are CE marked. In addition,Kreatech has obtained certificates for CE-marking of conformityfor our prenatal and PGD probes.All CE-marked FISH probes in this catalog are manufactured atKreatech Diagnostics facilities in Amsterdam, The Netherlands,and are labeled with ULS (Universal Linkage System).Manufacturing of all CE-marked products by Kreatech is carriedout according to international standards ISO 9001:2008 andISO 13485:2003 for which Kreatech holds certificates.Compliance to the European IVD Directive 98/79/EC, ISO9001:2008 and ISO 13485:2003 means that we are providinghigh quality in vitro diagnostic medical devices to be used fordiagnosis, prevention, monitoring, treatment, alleviation orinvestigation of disease, congenital disorders, physiologicaland/or pathological state of the human body without beingused in or on the human body.We strive to continuously improve the quality of these productsbased on the latest developments and techniques.CE marking & ISO Certificates115

Product IndexOncology probes - Hematology ProbesON = Oncology probesDescription Color Tests Cat# PageProduct Index116CML ON FIP1L1-CHIC2-PDGFRA (4q12) Del, Break red/green 10 KBI-10003 16ON PDGFRB (5q33) Break red/green 10 KBI-10004 17ON BCR/ABL t(9;22) Fusion red/green 10 KBI-10005 13ON BCR/ABL t(9;22) Fusion red/green 20 KBI-12005 13ON BCR/ABL t(9;22) TC, D-Fusion red/green/blue 10 KBI-10006 13ON FIP1L1-CHIC2-PDGFRA (4q12) Del, Break, TC red/green/blue 10 KBI-10007 16ON BCR/ABL t(9;22,) DC, S-Fusion, ES red/green 10 KBI-10008 14ON BCR/ABL t(9;22) DC, S-Fusion red/green 10 KBI-10009 14ON p53 (17p13) / MPO (17q22) “ISO 17q” green/red 10 KBI-10011 15CLL ON DLEU (13q14) / 13qter red/green 10 KBI-10102 18ON ATM (11q22) / SE 11 red/green 10 KBI-10103 19ON GLI (12q13) / SE 12 red/green 10 KBI-10104 21ON 6q21 / SE 6 red/green 10 KBI-10105 20ON C-MYC (8q24) / SE 8 red/green 10 KBI-10106 20ON ATM (11q22) / GLI (12q13) red/green 10 KBI-10108 22ON 6q21 / C-MYC (8q24) red/green 10 KBI-10109 23ON hTERC (3q26) / 3q11 red/green 10 KBI-10110 21ON p53 (17p13) / SE 17 red/green 10 KBI-10112 19ON p53 (17p13) / SE 17 red/green 20 KBI-12112 19ON DLEU (13q14) / p53 (17p13) red/green 10 KBI-10113 22ON p53 (17p13) / ATM (11q22) green/red 10 KBI-10114 23MDS ON MDS 7q- (7q22; 7q35) green/red 10 KBI-10202 26ON MDS 20q- (PTPRT 20q12) / 20q11 red/green 10 KBI-10203 27ON EVI t(3;3); inv(3) (3q26) Break red/green 10 KBI-10204 28ON EVI t(3;3); inv(3) (3q26) Break, TC red/green/blue 10 KBI-10205 28ON MDS 7q- (7q22; 7q35) / SE 7 TC green/red/blue 10 KBI-10207 27ON hTERT (5p15) / 5q31 red/green 10 KBI-10208 25ON MDS 5q- (5q31; 5q33) green/red 10 KBI-10209 25ON MDS 5q- (5q31; 5q33) / hTERT (5p15) TC green/red/blue 10 KBI-10210 26AML ON AML/ETO t(8;21) Fusion green/red 10 KBI-10301 29ON PML/RARA t(15;17) Fusion green/red 10 KBI-10302 30ON PML/RARA t(15;17) Fusion green/red 20 KBI-12302 30ON MLL (11q23) Break red/green 10 KBI-10303 30ON CBFB t(16;16), inv(16) Break red/green 10 KBI-10304 31ON RARA (17q21) Break red/green 10 KBI-10305 31ALL ON TEL/AML t(12;21) Fusion red/green 10 KBI-10401 32ON p16 (9p21) / 9q21 red/green 10 KBI-10402 33ON ETV6 (TEL) (12p13) Break red/green 10 KBI-10403 33MultipleMyelomaLymphomarelated probesON MM 11q23 / DLEU (13q14) green/red 10 KBI-10502 36ON MM 1q21 / 8p21 green/red 10 KBI-10503 37ON MM 15q22 / 6q21 green/red 10 KBI-10504 38ON MM 1q21 / SRD (1p36) green/red 10 KBI-10507 39ON MM 15q22 / 9q34 green/red 10 KBI-10508 38ON MM 19q13 / p53 (17p13) green/red 10 KBI-10509 37ON IGH (14q32) Break red/green 10 KBI-10601 24,39,42ON FGFR3/IGH t(4;14) Fusion green/red 10 KBI-10602 36ON MYC/IGH t(8;14) Fusion green/red 10 KBI-10603 40ON BCL1/IGH t(11;14) Fusion green/red 10 KBI-10604 41ON MYEOV/IGH t(11;14) Fusion green/red 10 KBI-10605 35ON BCL2/IGH t(14;18) Fusion green/red 10 KBI-10606 41ON BCL6 (3q27) Break red/green 10 KBI-10607 44ON MALT (18q21) Break red/green 10 KBI-10608 42ON CCND1 (BCL1;11q13) Break red/green 10 KBI-10609 43ON MAF/IGH t(14;16) Fusion green/red 10 KBI-10610 35ON MYC (8q24) Break, TC red/green/blue 10 KBI-10611 44

Oncology probes - Solid TumorsON = Oncology probesDescription Color Tests Cat# PageON ERBB2, Her-2/Neu (17q12) / SE 17 red/green 10 KBI-10701 47ON ERBB2, Her-2/Neu (17q12) / SE 17 red/green 50 KBI-14701 47ON EGFR, Her-1 (7p11) / SE 7 red/green 10 KBI-10702 59ON CC hTERC (3q26) C-MYC (8q24) / SE 7 TC red/green/blue 10 KBI-10704 50ON MYCN (2p24) / LAF (2q11) red/green 10 KBI-10706 52ON PPARγ (3p25) Break red/green 10 KBI-10707 51ON EWSR1 (22q12) Break red/green 10 KBI-10708 55ON hTERT (5p15) / 5q31 (tissue) red/green 10 KBI-10709 59ON p16 (9p21) / 9q21 (tissue) red/green 10 KBI-10710 50ON MLL (11q23) / SE 11 red/green 10 KBI-10711 53ON SRD (1p36) / SE 1(1qh) red/green 10 KBI-10712 53ON SYT (18q11) Break red/green 10 KBI-10713 56ON CHOP (12q13) Break red/green 10 KBI-10714 56ON FUS (16p11) Break red/green 10 KBI-10715 57ON FKHR (13q14) Break red/green 10 KBI-10716 57ON MDM2 (12q15) / SE 12 red/green 10 KBI-10717 58ON PTEN (10q23) / SE 10 red/green 10 KBI-10718 60ON C-MET (7q31) / SE 7 red/green 10 KBI-10719 60ON AURKA (20q13) / 20q11 red/green 10 KBI-10721 61ON AUKRB (17p13) / SE 17 red/green 10 KBI-10722 61ON TOP2A (17q21) / SE 17 red/green 10 KBI-10724 47ON CDK4 (12q13) / SE 12 red/green 10 KBI-10725 58ON TMPRSS2-ERG (21q22) Del, Break, TC red/green/blue 10 KBI-10726 63ON IGH (14q32) Break (tissue) red/green 10 KBI-10729 63ON BCL6 (3q27) Break (tissue) red/green 10 KBI-10730 64ON MALT (18q21) Break (tissue) red/green 10 KBI-10731 64ON ZNF217 (20q13) / 20q11 red/green 10 KBI-10733 48ON CCND1 (11q13) / SE 11 red/green 10 KBI-10734 62ON TOP2A (17q21) / Her-2/neu (17q12) / SE 17 TC red/green/blue 10 KBI-10735 48ON MDM4 (1q32) /SE 1 red/green 10 KBI-10736 54ON FGFR1 (8p12) Break red/green 10 KBI-10737 49ON p53 (17p13) / SE 17 (tissue) red/green 10 KBI-10738 65ON TFE3 (Xp11) Break red/green 10 KBI-10741 65Product Index117

Satellite Enumeration probesSE = Satellite Enumeration probes5x conc formatDescription Color Tests Cat# PageAll Human Centromer (AHC), RTU green or red 10 KBI-20000 84SE 1 (1qh) green, red, or blue 10 KBI-20001 84SE 2 (D2Z2) green, red, or blue 10 KBI-20002 84SE 3 (D3Z1) green, red, or blue 10 KBI-20003 84SE 4 (D4Z1) green, red, or blue 10 KBI-20004 84SE 6 (D6Z1) green, red, or blue 10 KBI-20006 84SE 7 (D7Z1) green, red, or blue 10 KBI-20007 84SE 8 (D8Z2) green, red, or blue 10 KBI-20008 84SE 9 (classical) green, red, or blue 10 KBI-20009 84SE 10 (D10Z1) green, red, or blue 10 KBI-20010 84SE 11 (D11Z1) green, red, or blue 10 KBI-20011 84SE 12 (D12Z3) green, red, or blue 10 KBI-20012 84SE 15 (D15Z4) green, red, or blue 10 KBI-20015 84SE 16 (D16Z2) green, red, or blue 10 KBI-20016 84SE 17 (D17Z1) green, red, or blue 10 KBI-20017 84SE 18 (D18Z1) green, red, or blue 10 KBI-20018 84SE 20 (D20Z1) green, red, or blue 10 KBI-20020 84SE X (DXZ1) green, red, or blue 10 KBI-20023 84SE Y (DYZ3) green, red, or blue 10 KBI-20024 84SE Y classical Q arm green, red, or blue 10 KBI-20025 84SE 1/5/19 green, red, or blue 10 KBI-20026 84SE 13/21 green, red, or blue 10 KBI-20027 84SE 14/22 green, red, or blue 10 KBI-20028 84SE X (DXZ1) / SE Y (DYZ3) green/red 10 KBI-20030 84SE 7 (D7Z1) / SE 8 (D8Z1) red/green 10 KBI-20031 84SE (X,Y,18) green/red/blue 10 KBI-20032 84* Add -G for Green, -R for Red, -B for Blue (available on request)Microdeletion probesMD = Microdeletion probesDescription Color Tests Cat# PageProduct IndexMD Miller-Dieker LIS (17p13 ) / Smith-Magenis RAI (17p11) red/green 10 KBI-40101 77MD DiGeorge “N25” (22q11) / 22q13 (SHANK3) red/green 10 KBI-40102 71,73MD DiGeorge Tuple (22q11) / 22q13 (SHANK3) red/green 10 KBI-40103 72,73MD DiGeorge T-box1 (22q11) / 22q13 (SHANK3) red/green 10 KBI-40104 72,73MD DiGeorge II (10p14) / SE 10 red/green 10 KBI-40105 73MD Cri-Du-Chat CTNND (5p15) / 5q31 red/green 10 KBI-40106 78MD Wolf-Hirschhorn WHSC1 (4p16) / SE 4 red/green 10 KBI-40107 78MD X-Inactivation XIST (Xq13) / SE X red/green 10 KBI-40108 79MD Prader-Willi SNRPN (15q11) / PML(15q24) red/green 10 KBI-40109 75MD Angelman UBE3A (15q11) / PML(15q24) red/green 10 KBI-40110 76MD Williams-Beuren ELN (7q11) / 7q22 red/green 10 KBI-40111 76MD Short Stature (Xp22) / SE X red/green 10 KBI-40112 79MD NSD1 (5q35)/ hTERT (5p15) red/green 10 KBI-40113 74MD NF1 (17q11) / MPO (17q22) red/green 10 KBI-40114 74MD STS (Xp22) / KAL (Xp22) / SE X TC red/green/blue 10 KBI-40115 80MD IGF1R (15q26) / 15q11 red/green 10 KBI-40116 81118

Whole Chromosome probes5x conc formatDescription Color Tests Cat# PageWhole Chromosome 1 green, red, or blue 5 KBI-30001 86Whole Chromosome 2 green, red, or blue 5 KBI-30002 86Whole Chromosome 3 green, red, or blue 5 KBI-30003 86Whole Chromosome 4 green, red, or blue 5 KBI-30004 86Whole Chromosome 5 green, red, or blue 5 KBI-30005 86Whole Chromosome 6 green, red, or blue 5 KBI-30006 86Whole Chromosome 7 green, red, or blue 5 KBI-30007 86Whole Chromosome 8 green, red, or blue 5 KBI-30008 86Whole Chromosome 9 green, red, or blue 5 KBI-30009 86Whole Chromosome 10 green, red, or blue 5 KBI-30010 86Whole Chromosome 11 green, red, or blue 5 KBI-30011 86Whole Chromosome 12 green, red, or blue 5 KBI-30012 86Whole Chromosome 13 green, red, or blue 5 KBI-30013 86Whole Chromosome 14 green, red, or blue 5 KBI-30014 86Whole Chromosome 15 green, red, or blue 5 KBI-30015 86Whole Chromosome 16 green, red, or blue 5 KBI-30016 86Whole Chromosome 17 green, red, or blue 5 KBI-30017 86Whole Chromosome 18 green, red, or blue 5 KBI-30018 86Whole Chromosome 19 green, red, or blue 5 KBI-30019 86Whole Chromosome 20 green, red, or blue 5 KBI-30020 86Whole Chromosome 21 green, red, or blue 5 KBI-30021 86Whole Chromosome 22 green, red, or blue 5 KBI-30022 86Whole Chromosome X green, red, or blue 5 KBI-30023 86Whole Chromosome Y green, red, or blue 5 KBI-30024 86* Add -G for Green, -R for Red, -B for Blue (available on request)Prenatal probesPN = Prenatal probesDescription Color Tests Cat# PagePN 13 (13q14) green 10 KBI-40001 68PN 21 (21q22) red 10 KBI-40002 68PN 13 (13q14) / 21 (21q22) green/red 10 KBI-40003 69SE 18 (D18Z1) 5x conc blue 10 KBI-20018-B 69SE X (DXZ1) / SE Y (DYZ3) green/red 10 KBI-20030 69SE 7 (D7Z1) / SE 8 (D8Z1) red/green 10 KBI-20031 69SE (X,Y,18) green/red/blue 10 KBI-20032 69PrenatScreen (13/21, X/Y18) green/red/blue 10 KBI-40005 69PrenatScreen (13/21, X/Y18) green/red/blue 30 KBI-40006 69PrenatScreen (13/21, X/Y18) green/red/blue 50 KBI-40007 69PloidyScreen (21, X, Y) red/green/blue 20 KBI-40008 69PreimpScreen PolB (13,16,18,21,22) five color 20 KBI-40050 67PreimpScreen Blas (13,18,21,X,Y) five color 20 KBI-40051 67MultiStar 24 FISH six color, 4 panels 10 KBI-40060 66MultiStar FISH Panel 1 six color 10 KBI-40061 66MultiStar FISH Panel 2 six color 10 KBI-40062 66MultiStar FISH Panel 3 six color 10 KBI-40063 66MultiStar FISH Panel 4 six color 10 KBI-40064 66Product Index119

Arm-Specific Probesready-to-useDescription Color Tests Cat# PageArm Specific Probe 1p green or red 5 KBI-30100 88Arm Specific Probe 1q green or red 5 KBI-30101 88Arm Specific Probe 2p green or red 5 KBI-30102 88Arm Specific Probe 2q green or red 5 KBI-30103 88Arm Specific Probe 3p green or red 5 KBI-30104 88Arm Specific Probe 3q green or red 5 KBI-30105 88Arm Specific Probe 4p green or red 5 KBI-30106 88Arm Specific Probe 4q green or red 5 KBI-30107 88Arm Specific Probe 5p green or red 5 KBI-30108 88Arm Specific Probe 5q green or red 5 KBI-30109 88Arm Specific Probe 6p green or red 5 KBI-30110 88Arm Specific Probe 6q green or red 5 KBI-30111 88Arm Specific Probe 7p green or red 5 KBI-30112 88Arm Specific Probe 7q green or red 5 KBI-30113 88Arm Specific Probe 8p green or red 5 KBI-30114 88Arm Specific Probe 8q green or red 5 KBI-30115 88Arm Specific Probe 9p green or red 5 KBI-30116 88Arm Specific Probe 9q green or red 5 KBI-30117 88Arm Specific Probe 10p green or red 5 KBI-30118 88Arm Specific Probe 10q green or red 5 KBI-30119 88Arm Specific Probe 11p green or red 5 KBI-30120 88Arm Specific Probe 11q green or red 5 KBI-30121 88Arm Specific Probe 12p green or red 5 KBI-30122 88Arm Specific Probe 12q green or red 5 KBI-30123 88Arm Specific Probe 13q green or red 5 KBI-30124 88Arm Specific Probe 14q green or red 5 KBI-30125 88Arm Specific Probe 15q green or red 5 KBI-30126 88Arm Specific Probe 16p green or red 5 KBI-30127 88Arm Specific Probe 16q green or red 5 KBI-30128 88Arm Specific Probe 17p green or red 5 KBI-30129 88Arm Specific Probe 17q green or red 5 KBI-30130 88Arm Specific Probe 18p green or red 5 KBI-30131 88Arm Specific Probe 18q green or red 5 KBI-30132 88Arm Specific Probe 19p green or red 5 KBI-30133 88Arm Specific Probe 19q green or red 5 KBI-30134 88Arm Specific Probe 20p green or red 5 KBI-30135 88Arm Specific Probe 20q green or red 5 KBI-30136 88Arm Specific Probe 21q green or red 5 KBI-30137 88Arm Specific Probe 22q green or red 5 KBI-30138 88Arm Specific Probe Xp green or red 5 KBI-30139 88Arm Specific Probe Xq green or red 5 KBI-30140 88Arm Specific Probe Yq green or red 5 KBI-30141 88Band Specific Probes - inquire green or red 20 KBI-302xx 88Product Index*Add -G for Green, -R for Red120

Sub-Telomeric probes5x conc formatDescription Color Tests Cat# PageSub Telomere 1pter green, red, or blue 5 KBI-40201 83Sub Telomere 1qter green, red, or blue 5 KBI-40202 83Sub Telomere 2pter green, red, or blue 5 KBI-40203 83Sub Telomere 2qter green, red, or blue 5 KBI-40204 83Sub Telomere 3pter green, red, or blue 5 KBI-40205 83Sub Telomere 3qter green, red, or blue 5 KBI-40206 83Sub Telomere 4pter green, red, or blue 5 KBI-40207 83Sub Telomere 4qter green, red, or blue 5 KBI-40208 83Sub Telomere 5pter green, red, or blue 5 KBI-40209 83Sub Telomere 5qter green, red, or blue 5 KBI-40210 83Sub Telomere 6pter green, red, or blue 5 KBI-40211 83Sub Telomere 6qter green, red, or blue 5 KBI-40212 83Sub Telomere 7pter green, red, or blue 5 KBI-40213 83Sub Telomere 7qter green, red, or blue 5 KBI-40214 83Sub Telomere 8pter green, red, or blue 5 KBI-40215 83Sub Telomere 8qter green, red, or blue 5 KBI-40216 83Sub Telomere 9pter green, red, or blue 5 KBI-40217 83Sub Telomere 9qter green, red, or blue 5 KBI-40218 83Sub Telomere 10pter green, red, or blue 5 KBI-40219 83Sub Telomere 10qter green, red, or blue 5 KBI-40220 83Sub Telomere 11pter green, red, or blue 5 KBI-40221 83Sub Telomere 11qter green, red, or blue 5 KBI-40222 83Sub Telomere 12pter green, red, or blue 5 KBI-40223 83Sub Telomere 12qter green, red, or blue 5 KBI-40224 83Sub Telomere 13qter green, red, or blue 5 KBI-40225 83Sub Telomere 14qter green, red, or blue 5 KBI-40226 83Sub Telomere 15qter green, red, or blue 5 KBI-40227 83Sub Telomere 16pter green, red, or blue 5 KBI-40228 83Sub Telomere 16qter green, red, or blue 5 KBI-40229 83Sub Telomere 17pter green, red, or blue 5 KBI-40230 83Sub Telomere 17qter green, red, or blue 5 KBI-40231 83Sub Telomere 18pter green, red, or blue 5 KBI-40232 83Sub Telomere 18qter green, red, or blue 5 KBI-40233 83Sub Telomere 19pter green, red, or blue 5 KBI-40234 83Sub Telomere 19qter green, red, or blue 5 KBI-40235 83Sub Telomere 20pter green, red, or blue 5 KBI-40236 83Sub Telomere 20qter green, red, or blue 5 KBI-40237 83Sub Telomere 21qter green, red, or blue 5 KBI-40238 83Sub Telomere 22qter green, red, or blue 5 KBI-40239 83Sub Telomere XYpter green, red, or blue 5 KBI-40240 83Sub Telomere XYqter green, red, or blue 5 KBI-40241 83* Add -G for Green, -R for Red, -B for Blue (available on request)Product Index121

Mouse FISHDescription Color Tests Cat# PageAll Mouse Centromere (AMC) red/green 10 KBI-30500 90TK (11qE1) / AurKa (2qH3) red/green 10 KBI-30501 90TK (11qE1) / WC Y red/green 10 KBI-30502 90RAB9B (XqF1) / DSCR (16qC4) red/green 10 KBI-30503 90RAB9B (XqF1) / WC Y red/green 10 KBI-30505 90CISHDescription Tests Cat# PageUniStar CISH Detection Kit 10 slides KBI-50001 92UniStar Her2/neu (17q12) 10 Tests KBI-50701 92UniStar EGFR (7p11) 10 Tests KBI-50702 92UniStar C-MET (7q31) 10 Tests KBI-50719 92TwinStar CISH Detection Kit 10 slides KBI-60010 92TwinStar Her2/neu (17q12) 10 Tests KBI-60701 92TwinStar EGFR (7p11) 10 Tests KBI-60702 92TwinStar C-MET (7q31) 10 Tests KBI-60719 92Kits and ReagentsDescription Contents Cat# PagePOSEIDON Tissue Digestion Kit II 5x5 slides KBI-60004 98POSEIDON FISH Reagent Kit 5x5 slides KBI-60005 98POSEIDON FISH Digestion Kit 5x5 slides KBI-60006 98POSEIDON Tissue Digestion Kit I 5x5 slides KBI-60007 98Igepal 5 ml LK-069A 99Rubber Cement, Fixogum 125 ml LK-071A 99DAPI Counterstain (0.1µg/ml) 500 µl LK-095B 99DAPI Counterstain (1µg/ml) 500 µl LK-096B 99Counterstain Diluent 500 µl LK-097B 99FISH Hybridization Buffer (FHB) 100 µl KBI-FHB 99Paraffin Tissue Buffer (PTB) 100 µl KBI-PTB 99Whole Chromosome Buffer (WCB) 50 µl KBI-WCB 99Product Index122

FISHBright Labeling KitsDescription Contents Cat# PageFISHBright 415 Blue for labeling 10 µg DNA FLK-001 100FISHBright 495 Green for labeling 10 µg DNA FLK-002 100FISHBright 505 Green for labeling 10 µg DNA FLK-003 100FISHBright 550 Red for labeling 10 µg DNA FLK-004 100FISHBright 547 Light Red for labeling 10 µg DNA FLK-005 100FISHBright 647 Far Red for labeling 10 µg DNA FLK-006 100FISHBright Biotin for labeling 10 µg DNA FLK-007 100FISH Grade CoT 500 µg KB-COT 101Cell culture media and accessoriesDescription Contents Cat# PageKREAvital Prenatal Medium (Basal) 90ml KBI-90010 94KREAvital Prenatal Medium (Basal) 450ml KBI-92010 94KREAvital Prenatal Medium (Supplement) 10ml KBI-90011 94KREAvital Prenatal Medium (Supplement) 50ml KBI-92011 94KREAvital Prenatal Medium (Complete) 100ml KBI-90012 94KREAvital Prenatal Medium (Complete) 500ml KBI-92012 94KREAvital Prenatal Medium PLUS (Complete) 100ml KBI-90013 94KREAvital Prenatal Medium PLUS (Complete) 500ml KBI-92013 94KREAvital Lymphocyte Karyotyping Medium (without PHA) 100ml KBI-90020 94KREAvital Lymphocyte Karyotyping Medium (without PHA) 500ml KBI-92020 94KREAvital Lymphocyte Karyotyping Medium (including PHA) 100ml KBI-90021 94KREAvital Lymphocyte Karyotyping Medium (including PHA) 500ml KBI-92021 94KREAvital Bone Marrow Karyotyping Medium 100ml KBI-90030 95KREAvital Bone Marrow Karyotyping Medium 500ml KBI-92030 95KREAvital Myeloid Cell Medium 100ml KBI-90031 95KREAvital Myeloid Cell Medium 500ml KBI-92031 95Colchicine Solution (10µg/ml, in PBS) 25ml KBI-90050 95Colcemid Solution (10µg/ml, in PBS) 10ml KBI-90051 95Potassium Chloride (0.075M) 100ml KBI-90052 96Phytohaemagglutinin M-Form 5ml KBI-90053 96Sodium Citrate Solution (0.8%) 500ml KBI-90054 96Trypsin EDTA 10X (EDTA 0.2%, Trypsin 0.5%, in saline solution) 20ml KBI-90055 96Trypsin EDTA 10X (EDTA 0.2%, Trypsin 0.5%, in saline solution) 100ml KBI-92055 96EquipmentDescription Contents Cat# PageThermoBrite (240V, 50 - 60Hz) TS-02 97Humidity Control Cards 10 HC-10 97Cytofuge2 (100 - 240V, 50 / 60 Hz) CF-02 97Product Index123

DNA LabelingDescription Reactions Cat# PageULS arrayCGH Labeling Kit (with Cy3 and Cy5) for labeling 2 x 20 µg DNA EA-005 104ULS arrayCGH Labeling Kit (with Cy3) for labeling 40 µg DNA EA-005A 104ULS arrayCGH Labeling Kit (with Cy5) for labeling 40 µg DNA EA-005B 104ULS cDNA Synthesis and Labeling Kit (with Cy3 and Cy5) for labeling 2 x 50 µg cDNA DSK-001 104ULS cDNA Synthesis and Labeling Kit (with Cy5) for labeling 100 µg cDNA DSK-002 104ULS cDNA Synthesis and Labeling Kit (with Cy3) for labeling 100 µg cDNA DSK-003 104ULS cDNA Synthesis and Labeling Kit (with Biotin) for labeling 100 µg cDNA DSK-004 104Nucleic Acid LabelingDescription Reactions Cat# PagePlatinumBright Nucleic Acid Labeling Kit (495 Green) for labeling 20 µg template GLK-001 109PlatinumBright Nucleic Acid Labeling Kit (547 Light Red) for labeling 20 µg template GLK-002 109PlatinumBright Nucleic Acid Labeling Kit (647 Far Red) for labeling 20 µg template GLK-003 109PlatinumBright Nucleic Acid Labeling Kit (550 Red) for labeling 20 µg template GLK-004 109PlatinumBright Nucleic Acid Labeling Kit (570 Red) for labeling 20 µg template GLK-005 109PlatinumBright Nucleic Acid Labeling Kit (415 Blue) for labeling 20 µg template GLK-006 109PlatinumBright Nucleic Acid Labeling Kit (Biotin) for labeling 20 µg template GLK-007 109RNA LabelingDescription Reactions Cat# PageULS microRNA Labeling Kit (with Cy3 and Cy5) for labeling 2 x 25 µg RNA EA-036 107ULS microRNA Labeling Kit (with Cy3) for labeling 50 µg RNA EA-037 107ULS microRNA Labeling Kit (with Cy5) for labeling 50 µg RNA EA-038 107ULS aRNA Labeling Kit (with Cy3 and Cy5) for labeling 2 x 50 µg aRNA EA-006 106ULS aRNA Labeling Kit (with Biotin for Affymetrix® Genechips®) for labeling 500 µg aRNA EA-010 106ULS aRNA Labeling Kit (with Biotin) for labeling 250 µg aRNA EA-018 106ULS Fluorescent Labeling Kit for Agilent arrays (with Cy3 and Cy5) for labeling 2 x 50 µg aRNA EA-021 107ULS Fluorescent Labeling Kit for Agilent arrays (with Cy5) for labeling 50 µg aRNA EA-022 107ULS Fluorescent Labeling Kit for Agilent arrays (with Cy3) for labeling 50 µg aRNA EA-023 107ULS Labeling Kit for CombiMatrix arrays (with Cy5) for labeling 125 µg aRNA EA-025 107ULS Labeling Kit for CombiMatrix arrays (with Biotin) for labeling 125 µg aRNA EA-027 107Product Index124

RNA Amplification and LabelingDescription Reactions Cat# Page(20 amplifications each)RNA ampULSe Amplification and Labeling Kit (with Cy3 and Cy5) for labeling 2 x 20 µg aRNA GEA-001 106RNA ampULSe Amplification and Labeling Kit (with Biotin for Affymetrix® Genechips®) for labeling 40 µg aRNA GEA-004 106RNA ampULSe Amplification and Labeling Kit (with Biotin) for labeling 200 µg aRNA GEA-006 106RNA ampULSe Amplification and Labeling Kit (with Cy3 and Cy5 for Agilent arrays) for labeling 2 x 20 µg aRNA GEA-014 106RNA ampULSe Amplification and Labeling Kit (with Cy5 for Agilent arrays) for labeling 40 µg aRNA GEA-016 106RNA ampULSe Amplification and Labeling Kit (with Cy3 for Agilent arrays) for labeling 40 µg aRNA GEA-018 106RNA ampULSe Amplification and Labeling Kit (with Cy5 for CombiMatrix arrays) for labeling 100 µg aRNA GEA-022 106RNA ampULSe Amplification and Labeling Kit (with Biotin for CombiMatrix arrays) for labeling 100 µg aRNA GEA-026 106Protein LabelingDescription Reactions Cat# PageTwo-color ULS Serum and Plasma Protein Labeling and Detection Kit 4 dual labelings PLK-001 108Two-color ULS Cell Lysate Protein Labeling and Detection Kit 4 dual labelings PLK-002 108PlatinumLink Protein Labeling Kit (BIO) 4 single labelings PLK-007 110PlatinumLink Protein Labeling Kit (FLU) 4 single labelings PLK-009 110PlatinumLink Protein Labeling Kit (RHO) 4 single labelings PLK-010 110Nucleic Acid CleanupDescription Reactions Cat# PageKREApure columns 20 pcs KP-020 111KREApure columns 50 pcs KP-050 111KREApure 96 1 plate KP-096 111Array-Grade KREAcot DNA 500 µg EA-020 105Array-Grade KREAcot DNA 10 mg EA-035 105Megapool Reference DNA, male 200 µg EA-100M 105Megapool Reference DNA, female 200 µg EA-100F 105Product Index125

How To OrderHow to place an orderOrders are accepted by phone, fax, email or mail.When placing an order please include the followinginformation:• Your account number (required)• Your name and phone number• Complete billing address• Complete shipping address• Purchase order number• Catalogue number and description of product• Quantity needed• VAT number (where applicable)If it is necessary to send a written order confirmation bymail or fax, please indicate clearly that your order is marked“CONFIRMATION”. This will assist in avoiding shipmentduplications. KREATECH cannot be held responsible in caseswhere the latter procedure is not followed.We accept Visa and MasterCardIf you wish to pay with a credit card please use the fax optionto send your order and please provide the name of your creditcard, account number, expiration date and security code whenplacing credit card orders.InternationalKreatech DiagnosticsVlierweg 20Phone: + 31 (0)20 6919181Email: customerservice@kreatech.com1032 LG AmsterdamFax: +31 (0)20 630 42 47Website: www.kreatech.comThe NetherlandsGermanyKreatech DiagnosticsFriedrichstrasse 50Phone: + 49 (0)30 8596 2361Email: customerservice@kreatech.com10117 BerlinFax: + 49 (0) 30 8596 2360Website: www.kreatech.comGermanyHow to orderFranceKreatech Diagnostics20 Avenue de la Paix67080 Strasbourg CedexFrancePhone: + 33 (0)1 4372 0079Fax: +33 (0)1 4348 8244Email: customerservice@kreatech.comWebsite: www.kreatech.com126

International DistributorsAlgeriaSalima MedicalMr. Salomon Moustafaoui3, rue Ahmed Benlounesse16606 El-Biar AlgerPhone: +021 79 10 94Fax: +021 79 10 94E-mail: salima_medical@hotmail.frAustraliaDiagnostic Technology Pty Ltd.Suite 45, 7 Narabang WayBelrose, NSW 2085Phone: + 61 2 99862011Fax: + 61 2 99862022E-mail:info@diagnostictechnology.com.auBelgiumAnnovum B.V.Hollands End 281244 NR AnkeveenThe NetherlandsPhone: + 31 (0)35 642 12 16Fax: + 31 (0)35 656 48 06E-mail: vragen@annovum.nlBrazilUniscience do BrasilAv. Cândido Portinari, 933/93705114-001 São Paulo - SPPhone: + 55 (0)11 3622 2320Fax: +55 (0)11 3622 23 23E-mail: info@uniscience.comBulgaria:Elta 90m O O D19, Dunav Str. Ent.A Fl.11000 SofiaPhone: + 359 2 983 9649Fax: + 359 2 983 2211CanadaVeridex, LLC1001 US HWY 202 SouthRaritan, NJ 08869USAPhone: 1-877-VeridexE-mail: bscsr2@ocdus.jnj.comChinaYou Ning Biotech Co. Ltd.7C, Run Yue Building Block 2. No.0,Tian He RoadGuangzhouPhone: +86 20 37604588Fax: +86 20 37604618E-mail: info@youning.comChinaWill-Tek Electro-Optical Ltd.2C, No. 1, Alley 889,Wuzhong RoadShanghaiPhone: 021-6406-4668Fax: 021-5422-5188E-mail: will-tek@will-tek.com.cnColombiaAndina de Tecnologías Ltda.Calle 34 No. 81-59MedellínPhone: +57 4 4164040Fax: +57 4 4164040E-mail: biotecno@anditecnica.comCroatiaJasika d.o.o.Remetineèka cesta 115,10000 ZagrebPhone: + 385 1 65 52 664Fax: + 385 1 65 35 018Email: ivana.tomicic@jasika.hrCzech RepublicIntimex s.r.o.Karvina-Nove MestoVrchlickeho sady 541/6735 06Tel: + 420 596 311612Fax: + 421 596 311018E-mail: intimex@post.czDenmarkAH Diagnostics ASRunefoften 188210 AarhusPhone: + 45 8745 9010Fax: + 45 8745 1292E-mail: ahdiag@ahdiag.dkEgyptCornell Lab3/1 Degla 5th SectorEl MaadiCairoPhone: + 202 25160732Fax: + 202 25200270E-mail: corlab@cornell-lab.com.egEstoniaQuantum Eesti ASSaekoja 36a50107 TartuPhone: + 372 7301321Fax: + 372 7304310E-mail: quantum@quantum.eeFinlandAH DiagnosticsKoetilantie 1 B 400790 HelsinkiPhone: + 358 9 3509100Fax: + 358 9 35091022E-mail: ahdiagnostics@ahdiagnostics.fiGreeceBioanalytica S.A.Biotechnology and Analytical Systems3-5 Iliddion Str.11528 AthensPhone: +30 210 6400318Fax: + 30 210 6462748E-mail: l.katabelisi@bioanalytica.grand orders@bionalytica.grHungaryBioMarker Ltd.2100 GödöllöSzölö utca 27 - 29.Tel: +36 28 419 986Fax +36 28 422 319E-mail: biomarker@biomarker.huIcelandMedProbeP.O.Box 2640 St.HanshaugenN-0131 OsloNorwayPhone: + 47 23 32 73 80Fax: + 47 23 32 73 90E-mail: medprobe@medprobe.comIndiaBioimaging Requisites1st Floor, Srisha Business Centre#1, 3rd Cross Lalbagh RoadBangalore - 560 027Phone: +91-98210 2437Fax: +91-80-2227 6118E-mail: rajeev@bio-image.comIranSakan TebNo 28, Akhavan St., Shariate Ave.Passed Junction of Ayatollah Sadr19316 TehranPhone: + 982 1 2223 3133Fax: +982 1 2221 4773E-mail: SakanTeb@hotmail.comIsraelBiological Industries Israel Ltd.Contact: Dr. Gary BennetKibbutz Beit HaemekM.P. AshratISRAEL, 25115Phone: + 972 4 996 05 95Fax: + 972 4 996 99 96E-mail: gary@bioind.comItalyResnova S.r.I.Via Cadore, 1400045 GENZANO di ROMA RMPhone: + 39 (0)6 93955058Fax: + 39 (0)6 93955059E-mail: servizioclienti@resnovaweb.itJapanFunakoshi Co. Ltd.9-7 Hongo 2-ChomeBunkyou-KuTokyo 113-0033Phone: + 81 3 5684 1620Fax: + 81 3 5684 1775E-mail: reagent@funakoshi.co.jpJordanLeanGeneP.O.Box 697 Tlaa AlaliAmmanPhone: + 962 6 46 55 401Fax: + 962 6 46 55 402E-mail: support@leangene-jo.comKoreaGeno Diagnostics Co. Ltd.RM B3, WooLim Lion's Valley Bldg.A 371-28Gasan-dong, Geumchun-guSeoulPhone: + 82 2 2026 5364Fax: + 82 2 744 5281E-mail: denis@genodiagnostics.co.krLatviaInterlux, SIALubãnas iela 78Rïga, LV-1073Phone: +371 67795240Fax: +371 67795241E-mail: info@interlux.lvLithuaniaLithuania Interlux Ltd.Avieciu 16, Vilnius 2021Phone: + 370 5 278 68 50Fax: + 370 5 279 67 28E-mail: spirit@interlux.ltMalaysiaNano Life Quest Sdn. Bhd.No.33, Jalan Puteri 5/10Bandar Puteri, 47100 PuchongSelangor D.E.Phone: + 603 8063 2688Fax: + 603 8063 2699E-mail: info@nanolifequest.comMéxicoUniparts S.A.Galileo 92, PolancoMéxico, D.F. 11550Phone: + 52 55 52 82 47 18Fax: + 52 55 52 81 47 22E-mail: benitor@uniparts.com.mxMoroccoScomedica22 Rue Mausolée,Résidence AbirQuartier des Hôpitaux 20100CasablancaPhone: +212 522 86 45 78Fax: +212 522 86 45 79E-mail: a.sqalli@scomedica.maThe NetherlandsAnnovum B.V.Hollands End 281244 NR AnkeveenPhone: + 31 (0)35 642 12 16Fax: + 31 (0)35 656 48 06E-mail: vragen@annovum.nlNorwayMedProbeP.O.Box 2640 St.HanshaugenN-1031 OsloPhone: + 47 23 32 73 80Fax: + 47 23 32 73 90E-mail: medprobe@medprobe.comPolandIntimex sp. z.o.o.Krzysztof StankiewiczIntimex sp.z.o.o.ul. Basniowa 302-349 WarszawaPhone: + 48 22 6686465Fax: +48 22 8221147E-mail: biuro@intimex.com.plPortugalBioportugalRua do Campo Alegre 13062° Sala 2084150-174 PortoPhone: + 351 22 6004800Fax: + 351 22 6004801E-mail: bioportugal@bioportugal.ptRomaniaDexter ComStr. Popa Rusu, nr. 9A, apt 6BucurestiPhone: +4-021-212.23.69Fax: +4-021-212-23.70E-mail: dexter@itcnet.roRussiaMedico-Diagnostic LaboratoryGamalai, 16Moscow, 123098Phone: + 499 190 28 68Fax: + 499 190 30 47E-mail: meddialab@mtu-net.ruSloveniaProbo d.o.o.Prekorje 48SI-3211 Škofja vasPhone: + 386 (0)3 4928741Fax: + 386 (0)3 4928741E-mail: gabrijel.popovic@probo.siSouth AfricaIepsa279 Brooklyn Rd, BrooklynPretoriaPhone: + 27 12 3622029Fax: + 27 12 3622030E-mail: iepsamed@iepsamed.co.zaSpainVitro S.A.Via de los Poblados, no 175a PlantaNaves 13 y 2Edifico Indubuilding28033 MadridPhone: + 34 913 82 16 20Fax: + 34 917 63 66 68E-mail: admvm@vitroweb.comSwedenMicro SystemÄlvkvarnsvägen 165S-163 51 SPÅNGAPhone: + 46 8 754 08 40Fax: + 46 8 754 0840E-mail: info@microsystem.seSyriaLeanGeneP.O.Box 697 Tlaa AlaliAmman, JordanPhone: + 962 6 46 55 401Fax: + 962 6 46 55 402E-mail: support@leangene-jo.comTaiwanMajor Instruments Co., Ltd9F. 69-3, Chung-Cheng E. Road, Sec. 2,Tanshui, TaipeiPhone: +866-2-2808-1452Fax: +866-2-2808-2354E-mail: major@major.com.twThailandDscience Company Ltd301/354 Ramkamhaeng 68Ramkamhaeng Rd, HuamarkBangkapiBangkok 10240Phone: + 66 (2) 729 0239Fax: + 66 (2) 729 0239 ext 0E-mail: info@dscience.co.thTunisiaBiomax Tunisie63 Avenue Abou Kacem Chebbi,Residence OmniaEscalier C, N°62080 ArianaPhone: +216 98349693Fax: +216 71710590E-mail: biomax.tunisie@planet.tnTurkeyTokra Medical Tic. Ltd. Sti.682. Sokak No: 1906370 OSTimAnkaraPhone: + 90 312 3956009Fax: + 90 312 3953961E-mail: import@tokra.com.trUnited KingdomCepheid UK Ltd.Stretton House, Highstairs LaneStretton, Derbushire DE55 6FDPhone: + 44 (0) 1246 860730Fax: +44 (0) 1246 866637E-mail: info@strettonscientific.co.ukUnited StatesVeridex, LLC1001 US HWY 202 SouthRaritan, NJ 08869Phone: 1- 877-VeridexE-mail: bscsr2@ocdus.jnj.comVietnamVinh Tien TechnologySolutions Co., Ltd.118/34/18/1 Lien Khu 5-6 Str.Binh Hung Hoa B wardBinh Tan DistrictHo Chi Minh CityPhone: + 84 9 3327 8868Fax: +84 (8) 6266 9209E-mail: info@vitechins.comInternational Distributors127

© 2010 KREATECH DiagnosticsPublished Januari 2010