2008 Barcelona - European Society of Human Genetics

Cancer genetics
P04.112
NBS 657del5 mutation in patients with myelodysplastic
syndromes (mDs)
B. Jekic 1 , L. Lukovic 1 , B. Popovic 2 , I. Novakovic 1 , J. Milasin 2 , T. Damnjanovic 1 ,
N. Maksimovic 1 , A. Bogdanovic 3 , V. Bunjevacki 1 ;
1 Institute of Human Genetics, School of Medicine, University of Belgrade, Belgrade,
Serbia, 2 Institute of Biology and Human Genetics, School of Dentistry,
University of Belgrade, Belgrade, Serbia, 3 Institute of Hematology, Clinical Center
of Serbia, Belgrade, Serbia.
Myelodysplastic syndromes (MDS) are the most common group of
hematological disorders in persons older than 60-year age . MDS are
characterized by elevated apoptosis in bone marrow and peripheral
blood cytopenias . Since more than one third of all MDS patients develop
acute leukemia MDS are considered preleukemic states .
NBS1 gene encodes for the nibrin (p95 protein) . p95 acts in a doublestrand
DNA break repair as the part of MRE11/RAD50 double-strand
break (DSB) repair complex . Nibrin is involved in cell cycle checkpoint,
meiotic recombinations and telomere maintenance .
NBS1 gene mutations are recognized as a main molecular event in
development of Nijmegen breakage syndrome (NBS) . NBS is chromosome
instability syndrome resulting in microcefaly, growth retardation,
immunodeficiency and predisposition to different types of cancer. NBS
patients have a particularly high predisposition to lymphoid malignancy
.
Independently from Nijmegen breakage syndrome, alterations of
NBS1 gene sequence (mostly nucleotide substitutions and deletions)
and expression are found in number of malignancies . Deletion of 5bp
in exon 7(657del5) is the most often NBS1 gene mutation found in
Slavic population (so-called Slavic mutation) .
In this study we have analyzed NBS1 657del5 mutation in a cohort
of 71 MDS patients . Patients DNA were obtained from bone marrow
microscope slides splices . To detect mutation we have compared PCR
products of MDS patients DNA with control DNA containing NBS1
657del5 mutation . Only one patient harbored mutation . According to
this study, NBS1 657del5 mutation may not be important event in evolution
of MDS .
P04.113
A pediatric mDs patient with 5q31 deletion
H. Acar1 , U. Calıskan2 , T. Cora1 , Ö. Balasar1 , C. Ucar2 ;
1Dept. of Medical Genetics, Meram Medical School, Selcuk University, Konya,
Turkey, 2Dept. of Pediatric-Hematology, Meram Medical School, Selcuk University,
Konya, Turkey.
Myelodysplastic syndrome (MDS) includes the ineffective proliferation
or production of cells in bone marrow (BM) leading to peripheral blood
cytopenia and a preleukemic state . The pathogenesis of MDS involve
a multistep process involving two or more genetic alterations that lead
to alteration in cellular function that cause clonal proliferation of an abnormal
stem cell . In the present study, we report on a childhood patient
with MDS . The patient had 5q31 deletion by conventional cytogenetics
and fulorescence in situ hybridization (FISH) analysis with a specific
FISH probe at the diagnosis . We present the clinical features, genetics
and immunologic analysis at the diagnosis and also followed-up
results .
P04.114
FisH studies in multiple myeloma patients
O. O. Yuregir 1 , F. I. Sahin 1 , Z. Yilmaz 1 , E. Kizilkilic 2 , S. Karakus 2 , H. Ozdogu 2 ;
1 Baskent University Faculty of Medicine Department of Medical Genetics,
Ankara, Turkey, 2 Baskent University Faculty of Medicine Department of Adult
Hematology, Ankara, Turkey.
Multiple Myeloma (MM) is a heterogeneous disease regarding its
clinical and genetic properties . Cytogenetic studies are valuable diagnostic
tools in MM patients both at the time of diagnosis and during
clinical follow up. Although conventional karyotyping is the first choice,
fluorescent in situ hybridization (FISH) is also important in detecting
abnormalities that cannot be detected by karyotype analysis . Conventional
cytogenetic analysis and FISH results of bone marrow samples
of 36 MM patients at the time of diagnosis have been evaluated in
the current study . Three probes for chromosome 13q (RB1, D13S319,
D13S25), one for 14q32 (IgH) and one for 17p13 (p53) have been
used for hybridization with fixed cells. Conventional cytogenetic results
revealed that 20 patients (55 .5%) had normal karyotypes, whereas 8
(22 .2%) had numerical or structural chromosomal abnormalities . We
did not find appropriate metaphases for chromosome analysis in 8
(22 .2%) patients . FISH analyses revealed at least one or more abnormal
results in 25 (69 .5%) cases, whereas 11(30 .5%) cases had no
abnormal findings. 14q32 rearrangement was the most common finding
in FISH analyses and has been detected in 21 cases (58 .3%) .13q
deletion and 17p deletion have been detected in 11 (30 .5%) and 5
(13 .9%) cases, respectively . In evaluating MM patients, FISH studies
including 14q32 and 17p13 chromosome regions may yield quite significant
results during clinical follow up of the disease which has a
multistep pathogenesis .
P04.115
Cytogenetic studies among patients with myelodysplastic/
myeloproliferative diseases
M. Khaleghian, C. Azimi;
Department of Genetics, Cancer Institute, Imam Khomeini Medical Cener,
School of Medicine, Medical Sciences / University of Tehran, Tehran, Islamic
Republic of Iran.
The myelodysplastic/myeloprolliferative diseases (MDS/MPD) are
clonal myeloid disorders that possess both dyspastic and proliferative
features . Clinical symptoms are caused by complications resulting
from cytopenia, dysplastic cells with abnormal function, leukemic
infiltration of various organ systems, fever and malaise.
We are reporting the chromosome studies among 34 patients which
referred to us with diagnosis of MDS/MPD by Hematologists/Oncologists
during the last 12 months . Chromosome preparations were obtained
from lymphocyte cultures and analyzed after GTG-banding and
HR-banding .
30 patients (88 .24%) showed normal karyotype . 4 patients (11 .76%)
had chromosome abnormalities .
Only one 67-year-old man patient who were diagnosed by MDS,
showed abnormal karyotpe of : mos 46, XY, add (20)(q) / 46, XY .
Three patients with diagnosis of MPD also showed chromosome aberrations
as follows : First patient was a 32-year-old woman and her
karyotype was : mos 46, XX, t (2, 11) (q33, q23) / 46, XX, del 2 q33
+7+9 -11+18 -X / 46,XX . Second one was a 56-year-old man with
karyotype:
mos 47, XY, +22 / 45, XY, -7 / 46, XY .
Third case was a 57-year-old man and had a karyotype of: mos 92,
XXYY / 46, XY .
All the patients did not have a Philadelphia chromosome .
P04.116
cytogenetic study of 25 myelodysplastic syndrome
M. D. Souto, R. Pinto Leite, M. Cunha, M. Guerra, E. Ribeiro;
Centro Hospitalar de Tras-os-Montes e Alto Douro, Vila Real, Portugal.
The myelodysplastic syndromes (MDS) are a heterogeneous group
of clonal hematopoietic stem cell disorders . Cytogenetic analyses in
bone marrow samples of MDS patients have both pathophysiologic
significance and prognostic implications. Chromosomal abnormalities
are found in 40 - 70 % of the patients with MDS, and the characteristic
chromosomal abnormalities are del(5q), -5, del(7q), -7, +8, del(11q),
del(12p), del(13q), del(17p), del(20q), +21 .
We analyzed cytogenetically twenty five samples of MDS patients.
There were 12 female and 13 male patients with an age-range of 51
to 87 (median 69) . Cytogenetic abnormalities were observed in 40%
of patients . The most common abnormalities were monosomy of chromosome
7 and trisomy of chromosome 8 . Complex karyotypes were
found in 3% of the cases .
Despite the small number of cases studied the results obtained corroborate
those described in the literature and the importance of the
cytogenetic study in the prognosis of MDS .
P04.117
Role of JAK2 V617F mutation in myeloproliferative disorders
B. Kumar, V. Sharma, S. K Hasan, S. Sazawal, B. Sharma, R. Kumar, R. Saxena;
All India Institute of Medical Sciences, New Delhi, India.
Chronic Myeloproliferative disorders (MPD) polycythaemia vera(PV),
essential thrombocythaemia(ET), and idiopathic myelofibrosis(IMF)
form a range of clonal haematological malignant diseases characterized
by proliferation of one or more lineages of the myelo-erythroid se-