2008 Barcelona - European Society of Human Genetics

Cancer genetics
P04.081
Discordance between morphological and cytogenetical
remission in a patient with AmL and t(2;11)(p21;q23)
W. G. Kroes1 , E. den Ouden1 , M. Baasten1 , J. Kerkhoffs2 , R. Willemze1 ;
1 2 Leiden University Medical Center, Leiden, The Netherlands, Haga Hospital,
the Hague, The Netherlands.
We report here on a 58 year old male presenting with biphenotypical
acute myeloblastic leukemia .Conventional cytogenetic techniques on
bone marrow at initial diagnosis, before treatment, showed the following
karyotype:
4 6 , X Y, t ( 2 ; 11 ) ( p 2 1 ; q 2 3 ) , d e l ( 5 ) ( q 2 1 ) , a d d ( 1 2 ) ( p 1 2 ) [ 9 ] /
46,XY,t(2;11)(p21;q23)[5]/46,XY[1] .
FISH analysis with a DNA probe for the MLL-gene demonstrated
that the breakpoint at 11q23 was telomeric to the MLL gene . T(2;11)
(p21;q23) is a rare but recurrent translocation observed in MDS and
AML. This translocation is specifically associated with a deletion of
the long arm of chromosome 5 . After induction treatment the patient
was in complete morphological remission . However, cytogenetic studies
revealed the t(2;11) in all metaphases, without the del(5q) and
the add(12p) . Evaluation after the second therapy cycle showed again
a complete morphological remission but persistence of t(2;11) in all
analyzed metaphases . To investigate the possibility of a constitutional
chromosome aberration chromosomal analysis was performed on skinfibroblasts
and peripheral blood. The skin-fibroblasts revealed a normal
karyotype in all 100 analyzed metaphases . PHA stimulated blood
showed a mosaic karyotype : 46,XY,t(2;11)(p21;q23)[11]/46,XY[21] .
This suggests that the t(2;11) is an acquired aberration that persists in
spite of morphological remission .
The patient underwent a bone marrow transplantation and is still in
complete morphological remission after 10 months .
To our knowledge this is the first description of an AML case with a
t(2;11) showing discordant morphological and cytogenetical remission
.
P04.082
A pediatric case with atypical CML with ETV6/PDGFRB fusion
gene
A. V. Divane 1 , M. Baka 2 , D. Bouhoutsou 2 , A. Pourtsidis 2 , M. Varvoutsi 2 , D.
Doganis 2 , K. Koronioti 1 , H. Kosmidis 2 ;
1 Department of Cytogenetics, Locus Medicus, Diagnostic Centre, Athens,
Greece, 2 Department of Oncology, Aglaia Kyriakou Children Hospital, Athens,
Greece.
Atypical chronic myelogenous leukemia (aCML) is a leukemic disorder
that exhibits both myelodysplastic and myeloproliferative features at
the time of diagnosis . The median age of this rare disorder has been
reported to be in the seventh or eighth decade of life . Herein we report
a rare pediatric case of a 14 months old boy who was presented
with leukocytosis and frequent infections since the age of 6 months .
Bone marrow showed marked myeloid hyperplasia with elements
of dysplasia, particularly in eosinophil series . Conventional and molecular
cytogenetic analysis of BM were performed . FISH analysis for
chromosome abnormalities, commonly observed, in MDS/MPD were
performed using the appropriate probes, such as LSI BCR/ABL, CEP
8, LSI CBFB, LSI D205108 and LSI D7S486/CEP7 (Vysis) . FISH results
revealed normal hybridization pattern for all the chromosomes
analysed . Conventional cytogenetic analysis revealed a clone of
46,XY,t(5;12)(q33;p13) . RT-PCR analysis for the detection of the fusion
gene ETV6/PDGFRB was positive . In addition, FISH analysis using
the ETV6 (12p13) split probe (Vysis), confirmed the translocation
t(5;12)(q33;p13). With the above findings patient was diagnosed as
aCML with Philadelphia chromosome negative and BCR/ABL fusion
gene negative . The patient was treated with Gleevec (imatinib) for 8
months, achieved complete heamatological and cytogenetic remission
(MRD of 0,4% in the latest sample) and underwent MUD bone marrow
transplantation .
P04.083
BCR/ABL negative myeloproliferative neoplasms- cytogenetic
and molecular study
G. Cardos 1,2 , A. Arghir 1 , C. Diaconu 3 , M. Chivu 3 , L. Dragomir 3 , A. R. Lupu 4 , M.
Closca Gheorghiu 5 , D. Mut-Popescu 4 , M. E. Hinescu 1,4 , A. Lungeanu 1 ;
1 ”Victor Babes” National Institute, Bucharest, Romania, 2 Institute of Human
Biology, University of Hamburg, Hamburg, Germany, 3 ”Stefan Nicolau” Institute
of Virology, Bucharest, Romania, 4 ”Carol Davila” University of Medicine and
Pharmacy, Bucharest, Romania, 5 Coltea Clinical Hospital, Bucharest, Romania.
Myeloproliferative neoplasms (MPNs) originate in hematopoietic stem
cell compartment and exhibit a consistent phenotipic diversity . Only a
small fraction of patients harbour cytogenetic abnormalities (+8, +9,
20q-, 13q-, 12p-). The recent identification of JAK2 V617F mutation
as a key genetic event in a majority of cases has greatly advanced
the understanding of pathogenetic mechanisms in BCR/ABL negative
MPNs .
Our study has been focused on cytogenetic and molecular characterization
of BCR/ABL negative MPNs, with emphasis on correlation
between cytogenetic changes and JAK2 mutation status .
Chromosome analysis, FISH and RT-PCR (Revers-Transcription PCR)
have been used to investigate the BCR/ABL fusion and MPN-asocciated
genomic reccurrent abnormalities in 28 patients by date, diagnosed
with MPNs . Chromosome analysis was performed on cultured bone
marrow cells (GTG banding) . To detect cryptic chromosomal changes
(13q14, 17p13 .1, 20q12-13 deletions) interphase and metaphase FISH
with various LSI probes (Vysis) and Microsatellite PCR (D20S206 and
D20S119 Markers) were performed. Allele-specific PCR have been
used to detect the JAK2 V617F mutation .
All 28 patients displayed BCR/ABL negative status . The JAK2 V617F
mutation has been detected in 16 patients . The cytogenetic analysis
revealed chromosomal anomalies in 4 patients (trisomy 8, complex
cytogenetic changes) . No loses at investigated loci were found (13q14,
17p13 .1) . All patients were heterozygous for at least one of the two
DNA markers .
Further investigations will be performed in order to reveal other genetic
abnormalities, thus, we hope to contribute both in more precise diagnosis
and novel, patient-tailored therapeutic strategies .
Acknowledgements: National Program Research of Excellence, Project
111/2006 .
P04.084
microhomologies and interspersed repeat elements at genomic
breakpoints in chronic myeloid Leukemia
E. Mattarucchi 1 , V. Guerini 2 , A. Rambaldi 2 , L. Campiotti 3 , A. Venco 3 , F. Lo
Curto 1 , F. Pasquali 1 , G. Porta 1 ;
1 Department of Experimental and Clinical Biomedical Sciences, Università
dell’Insubria, Varese, Italy, 2 Hematology Unit, Ospedali Riuniti,, Bergamo, Italy,
3 Department of Clinical Medicine, Università dell’Insubria, Varese, Italy.
Reciprocal translocation t(9;22) is central to the pathogenesis of chronic
myeloid leukemia . Some authors have suggested that Alu repeats
facilitate this process, but supporting analyses have been sparse and
often anecdotal . The purpose of this study is to analyze the local structure
of t(9;22) translocations, and asses the relevance of interspersed
repeat elements at breakpoints . Collected data have been further compared
to the current models of DNA recombination, in particular the
Single-Strand Annealing (SSA) and the Non-Homologous End Joining
(NHEJ) processes . We proposed a protocol for the rapid characterization
of patient-specific genomic junctions, and we considered a total
of 27 patients diagnosed with chronic myeloid leukemia . Sequences
analysis reveals microhomologies at the junctions of 21 patients of
27, while interspersed repeats were of relevance (p