Novel genetic and epigenetic alterations in ... - Ous-research.no

More documents

Recommendations

Info

RØYRVIK ET AL.the PubMed database; search terms were compositions of mononucleotide, microsatellites,repeats, genes, frameshift, and the MeSH term neoplasms. From therelevant articles, with the cut-off date for inclusion being December 2006, mutationfrequency data for genes with coding microsatellites (or microsatellites in intronsand UTRs, as mentioned below) was pooled. Included were studies on MSItumors and cell lines of all tissue types in which the MSI phenotype occurs, theoverwhelming majority being gastrointestinal and endometrial tumors. Inclusionof mutation data on cell lines was kept to a minimum, as cell lines cannot be usedto represent the situation in primary tumors with regard to the frequencies offrameshift mutations of this type. 44,49 Table I encompasses those genes and studiessuitable for pooling, across tissue types but with particular attention to sporadic,primary colorectal tumors.TABLE IMutation frequencies of microsatellite-containing genesGene symbol—the most common name for any given gene in the scientific corpussurveyed; HGNC symbol—the name approved by the Human Genome NomenclatureCommittee, updated to October, 2007; Repeat—the repeat unit andnumber of units of microsatellites that were tested; Gene location—the location ofthe repeat within the gene, taken when possible from the scientific corpus, otherwisefrom Ensembl Exon View of a representative transcript; Chr. Location—the location of the gene on a chromosome, taken when possible from the scientificcorpus, otherwise from Ensembl or GeneCards.org; Mut%(tot)—the mutationfrequency across all studies of any microsatellite unstable tumor type; Mut S/C—the number of mutated samples across studies of colorectal carcinomas (mostlysporadic, but with HNPCC cases and cell lines where these could not be separated)over the total number of samples; Mut% S/C—the mutation frequencyacross studies of colorectal carcinomas (mostly sporadic, but with HNPCC casesand cell lines where these could not be separated); Ref—Articles from which mutationfrequency information was pooled.Gene HGNC RepeatChr. Location(tot)%(S/C)Mut %MutMut. S/CRefs.ABCF1 ABCF1 (A)10 6p21.33 29 % 17/58 29 %44,52AC1 C4orf6 (T)10 4p16.2 68 % 14/20 70 %53,54ACTRII ACVR2A (A)8 2q22.3 70 % 95/140 68 %55-59AD7c-NTP (T)8 1p36 6 % 2/35 6 %55AIM2 AIM2 (A)10 1q22 52 % 46/81 57 %44,55,56AMYB MYBL1 (A)8 8q22 11 %56ANG2 ANGPT2 (A)9 8p23.1 4 % 2/57 4 %49APAF-1 APAF1 (A)8 12q23 8 % 5/79 6 %60-62ATM ATM (T)7 11q22-23 13 % 4/44 9 %63-65ATR ATR (A)10 3q23 23 % 55/252 22 %17,44,49,53,66,67AXIN2 AXIN2(G)7,59,68,6917q24.1 20 % 18/81 22 %(C)6,(A)6,(C)5234
TARGET GENES OF MSI COLORECTAL CANCERBAX BAX (G)8TABLE I, continuedMutation frequencies of microsatellite-containing genesMutChr. LocationS/C %(S/C)Mut. MutGene HGNC Repeat%(tot)BAT1 BAT1 (T)8 6p21.3 16 %19q13.3-q13.4542 %359/773BCL10 BCL10 (A)8 1p22 8 % 14/172 8 %45 %BLM BLM (A)9 15q26.1 16 % 51/373 14 %BLYM (A)8 4q28.1 5 % 5/96 5 %BRCA1 BRCA1 (A)8 17q21 2 % 3/126 2 %BRCA2 BRCA2 (A)8 13q12.3 2 % 6/191 3 %CANX CANX (T)8 5q35.3 21 %CASP1 CASP1 (A)8 11q23 4 % 0/78 0 %CASP4 CASP4 11q22.3 0 % 0/9 0 %CASP5 CASP5 (A)1011q22.2-q22.343 % 94/207 45 %CBL CBL (ATG)6 11q.23.3 12 % 1/11 9 %CBP* CREBBP (C)5 16p13.3 86 % 86 %CCDC28A CCDC28A (A)8 6q24.1 10 % 3/41 7 %CCKBR CCKBR (T)811p15.4-p15.519 % 2/15 13 %CDC25C CDC25C (A)8 5q31.2 11 % 10/93 11 %CDX2 CDX2 (G)7 13q12.2 2 % 1/81 1 %CEBPZ CEBPZ (A)9 2p22.2 14 % 20/148 14 %CHD2 CHD2 (A)10 15q26 12 % 7/58 12 %CHK1 CHEK1 (A)9 11q24.2 9 % 9/68 13 %CRSP3 MED23 (T)86q22.33-q24.13 % 1/38 3 %CYSLT1 CYSLTR1 (A)8 Xq21.1 9 % 4/44 9 %DD5 EDD1 (A)8 8q22 25 %DNA-PKcs PRKDC (A)10 8q11.21 22 % 50/228 22 %Doc-1 FILIP1L 3q12.1 2 % 1/57 2 %DRP INPPL1 (C)8 11q13.4 4 % 2/42 5 %DSTN DSTN (T)8 20p12.1 12 % 4/42 10 %E2F-4 E2F4 (CAG)13* 16q21-22 47 % 50/111 45 %EIF5 EIF5 (CAC)7 14q32.32 0 % 0/11 0 %ELAVL3 ELAVL3 (G)9 19p13.2 37 % 7/19 37 %EP300 EP300 (A)5, (A)7 22q13.2 57 % 4/7 57 %EPHB2 EPHB2 (A)91p36.1-101/2441 %p35641 %ERCC5 ERCC5 (A)9 13q33.1 9 % 8/93 9 %F8 (A)8 * 2 Xq28 15 % 6/41 15 %FACE-1 ZMPSTE24 (T)9 1p34.2 8 % 3/37 8 %Refs.5646,49,53,55,56,59,62,67,70-10960,66,95,10517,49,55,59,64,66,67,90,96,110,1116617,64,71,11017,49,71,102,1105656,62,719417,44,49,53,59,62,87,99,106,10796,11011255,561136659,62,11449,66,11544,5284,94,1021055554,5644,49,53,61,66,67497155,5673,92,94,99,103,109,116,11711052,5411211861,665555235
Page 1 and 2:
Novel genetic and epigenetic altera
Page 3 and 4:
TABLE OF CONTENTSACKNOWLEDGEMENTS .
Page 5 and 6:
ACKNOWLEDGEMENTSThe present work ha
Page 7 and 8:
Prefacetechnology[3]. This new tech
Page 10 and 11:
SummaryThe subgroup of carcinomas w
Page 12 and 13:
Introduction“Epigenetic inheritan
Page 14 and 15:
Introductionamino acid change it is
Page 16 and 17:
Introductionmethylation during embr
Page 18 and 19:
IntroductionDNA is most of the time
Page 20 and 21:
IntroductionFigure 5. DNA methylati
Page 22 and 23:
IntroductionFigure 6. Incidence rat
Page 24 and 25:
IntroductionFigure 8. Tumor staging
Page 26 and 27:
Introductioninasmuch as 80% of colo
Page 28 and 29:
IntroductionInstabilities involved
Page 30 and 31:
Introductionthere seems to be a fid
Page 32 and 33:
Introductionsevere alterations are
Page 34 and 35:
Introductionpopulation-wide screeni
Page 36 and 37:
IntroductionFigure 12. Present and
Page 38 and 39:
RESULTS IN BRIEFPaper Ia. “DNA hy
Page 40 and 41:
Results in Briefinstability, and se
Page 42 and 43:
Results in BriefUnivariate survival
Page 44 and 45:
Discussionseveral factors, and full
Page 46 and 47:
Discussionlow threshold, we increas
Page 48 and 49:
DiscussionIt may seem like unnecess
Page 50 and 51:
Discussionthan 96% DHPLC do not sta
Page 52 and 53:
DiscussionFigure 13. Mutation detec
Page 54 and 55:
DiscussionClinical impact of molecu
Page 56 and 57:
Discussionmarkers with a very high
Page 58 and 59:
Discussionchromosomes in metaphase[
Page 60 and 61:
DiscussionThese examples underline
Page 62 and 63:
Discussiongenes. One is based on mu
Page 64 and 65:
CONCLUSIONSWe have identified novel
Page 66 and 67:
Future PerspectivesMolecular risk a
Page 68 and 69:
REFERENCES1. Breasted J (1930) The
Page 70 and 71:
References29. Deng G, Chen A, Pong
Page 72 and 73:
References57. Al-Sukhni W, Aronson
Page 74 and 75:
References84. Kunkel TA (1993) Nucl
Page 76 and 77:
ReferencesLeggett B, Levine J, Kim
Page 78 and 79:
References133. Lind GE, Thorstensen
Page 80 and 81:
References156. Meling GI, Lothe RA,
Page 82 and 83:
ReferencesT, Song X, Day RH, Sledzi
Page 84 and 85:
References196. Honda S, Haruta M, S
Page 86 and 87:
ORIGINAL ARTICLESAPPENDIXAppendix I
Page 89 and 90:
GASTROENTEROLOGY 2007;132:1631-1639
Page 91:
Paper IbGuro E Lind, Terje Ahlquist
Page 94 and 95:
Journal of Translational Medicine 2
Page 96 and 97:
Page 98 and 99:
Page 100 and 101:
Page 102 and 103:
Page 105:
Paper IITerje Ahlquist, Guro E Lind
Page 108 and 109:
BackgroundMost cases of colorectal
Page 110 and 111:
ADAMTS1 CDKN2A CRABP1 HOXA9 MAL MGM
Page 112 and 113:
pseudogene, leading to a high rate
Page 114 and 115:
strands. Proc Natl Acad Sci U S A 1
Page 116 and 117:
concomitant absence of transcript a
Page 119 and 120: Volume 10 Number 7 July 2008 pp. 68
Page 121 and 122: 682 RAS Signaling in Colorectal Car
Page 127: Table W2. Detailed Somatic Events o
Page 131 and 132: Identification of RCC2 as a prognos
Page 133 and 134: INTRODUCTIONMicrosatellite instabil
Page 135 and 136: unselected series of primary tumors
Page 137 and 138: specificity, i.e. that they only am
Page 139 and 140: On the assumption that DNA repair a
Page 141 and 142: In order to ensure that gene mutati
Page 143 and 144: Figure 2. Mutation frequency differ
Page 145 and 146: and TAF1B (0.50), ACVR2A and ASTE1
Page 147 and 148: Multivariate analysesA multivariate
Page 149 and 150: When comparing our findings of muta
Page 151 and 152: The test series included a low numb
Page 153 and 154: entering M-phase remains to be seen
Page 155 and 156: 12. Duval A, Reperant M, Hamelin R
Page 157 and 158: 34. Martineau-Thuillier S, Andreass
Page 159: AppendicesAppendix I:List of abbrev
Page 163 and 164: Critical Reviews TM in Oncogenesis,
Page 165 and 166: TARGET GENES OF MSI COLORECTAL CANC
Page 167: TARGET GENES OF MSI COLORECTAL CANC
Page 191: TARGET GENES OF MSI COLORECTAL CANC
show all

Novel genetic and epigenetic alterations in ... - Ous-research.no

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?