2009 Vienna - European Society of Human Genetics

Cancer genetics
is hTERC gene amplification detectable by FISH in acute myeloid leukemia
(AML) cells. The bone marrow samples of 23 newly diagnosed
adult AML patients were retrospectively analyzed for this study. We did
not detect a visible abnormality of the 3q region with the previous conventional
cytogenetic analyses of the patients. Interphase cells were
hybridized with hTERC (3q26) / 3q11 probe (Kreatech, Netherlands).
We did not detect amplification of the region in patients. Although it has
been reported that hTERT gene amplification may partially contribute
to the increased telomerase expression and activity in leukemic cells,
it is not possible to make such a conclusion with a small number of
patients with the results of the current study, as we did not detect amplified
hTERC in our group of patients.
P06.182
High resolution cytogenetic analysis of a clonal der(2)t(1;2)(q31.
2;q24.1) in an acute myeloid leukaemia
G. Gemayel1 , A. Aboura2 , A. C. Tabet2 , M. Maurin2 , B. Benzacken2 , K. Yakoubi2 ,
A. Baruchel2 , J. Marie3 , S. Haiat3 , B. Riou3 , F. Viguie3 ;
1 2 Hopital Robert Debré, Paris, France, Robert debré, Bd Sérurrier, France,
3Hotel Dieu, Place du Parvis Notre Dame, Paris, France.
A 25-year old woman was admitted for an acute myeloid leukaemia,
AML-M2 according to FAB classification. Bone marrow karyotype
at diagnosis showed an unbalanced reciprocal translocation
der(2)(t(1;2)(q?31;q2?3) as sole clonal abnormality, in major part of
mitoses. This rearrangement was not known as recurrent, leading to
a partial trisomy 1q and monosomy 2q of undefinite prognosis. After a
primary resistance to induction chemotherapy, a complete remission
was obtained and patient could benefit from a bone marrow transplantation.
She is still in remission at 1 year post diagnosis.
Breakpoints 1q and 2q of the translocation were precisely defined by
CGH array with a Perkin Elmer 5200 BAC clones chip, in order to detect
a potential new fusion gene. The study performed from diagnosis
bone marrow which contained 61% blast cells, confirmed the 1q and
2q imbalance, with breakpoints at 1q31.2 and 2q24.1. A FISH analysis
was performed with BAC probes of the ship, located the closer
from both breakpoints. 2q24.1BAC probe was deleted on der(2) but
1q31.2 BAC probe which covers 3 coding genes was entirely retained
by der(2). Investigations with other probes covering the breakpoint region
are in progress.
P06.183
Detection and Assessment of prognostic significance of ALK
gene rearrangement in NHL patients
H. F. I. A. Kayed 1 , Mona Wahba2, Amany Osman2, Manal Ismaeil2, Dina
Adel2, Amal Mahmoud1., M. Wahba 2 , A. Osman 2 , M. Ismaeil 2 , D. Adel 2 , A.
Mahmoud 1 ;
1 National Research Centre, Cairo, Egypt, 2 Ain Shams University, Cairo, Egypt.
The non random genetic aberrations in non Hodgkin lymphoma (NHL)
involving anaplastic lymphoma kinase (ALK) gene, t(2;5)(p23;q35)
creates NPM-ALK fusion gene, with tyrosine kinase activity responsible
for its oncogenic property; by activation of downstream effectors
such as phospholipase C. Thus this work aimed to detect ALK gene
(2p23) rearrangement in various types of NHL by conventional cytogenetics
(CC) and fluorescence in situ hybridization techniques (FISH),
and to compare between the results of both techniques. To delineate
this aim, ALK gene rearrangement was investigated in 25 newly diagnosed
grade IV adult NHL patients. FISH analysis revealed positive
ALK rearrangement in 5 (20%) cases, 4 of them were diagnosed as
anaplastic lymphoma and one as DLBCL in comparison to absolute
negative detection of t(2;5)(p23;q35) by CC; proving the superiority of
FISH in detection of specific genetic aberrations. According to the results
of FISH analysis, patients were divided into: Group I: with normal
ALK signals, Group: II with ALK aberrations.
In conclusion, ALK gene rearrangement was detected in NHL patients
with different histopathological subtypes, showing maximum expression
in ALCL. It was correlated with good patient outcome, indicating
its importance as an important prognostic factor and its potential
as a promising target for therapeutic intervention. FISH technique
possessed the upper hand in detection of ALK rearrangements as
an example of specific targeted aberrations in comparison to CCA.
Nevertheless, conventional karyotyping remained the cornerstone in
cytogenetic analysis because of its ability to simultaneously scan for
various aberrations affecting many chromosomal loci.
P06.184
chromosomal abnormalities in 50 patients with B-cell chronic
lymphocytic leukemia detected by array comparative genomic
hybridization
H. Urbankova, M. Holzerova, R. Plachy, Z. Pikalova, T. Papajik, K. Indrak, M.
Jarosova;
Department of Hemato-oncology, University Hospital and Palacky University
Olomouc, Olomouc, Czech Republic.
B-cell chronic lymphocytic leukemia (B-CLL) is the most common adult
leukemia. The progress in molecular genetic characterization of B-CLL
confirmed the prognostic role of IgV H mutational status, as well as
chromosomal abnormalities defined by molecular cytogenetic methods.
However, besides chromosomal changes with known prognostic
impact, such as deletions of 6q, 11q (ATM), 13q, 17p (TP53) detected
routinely, the other additional abnormalities can be found. It is presently
not clear whether these aberrations have any impact on prognosis
and disease progression. To detect abnormalities escaping from routine
FISH investigation, we performed array comparative genomic hybridization
(arrayCGH) of 50 B-CLL patients diagnosed recently in our
center. The aim of this study was supported by the fact, that gains and
losses of genetic material can lead either to oncogenic activation of
protooncogenes or to loss of tumor-suppressor genes function, within
the gained and deleted regions respectively. ArrayCGH revealed copy
number changes in 43 out of 50 patients. Except already well known
changes as 6q- (7 pts.), 11q- (13 pts.), 13q- (28 pts.), 17p- (5 pts.) and
+12 (5 pts.), we detected also other recurrent abnormalities as 2p+ (11
pts.), 8q+ (4 pts.), 14q- (3 pts.), abnormalities of chromosome 18 (9
pts.) and others. Cases with detected 6q- were subjected to 32K tiling
path chromosome 6 arrayCGH in order to define the minimal commonly
deleted region more precisely. We will present a summary of
cytogenetic, FISH and arrayCGH findings in 50 B-CLL patients.
This work is supported by grant NR 9484 and MSM 6198959205.
P06.185
chromosomal abnormalities in patients with B-cell chronic
lymphocytic leukaemia from a single center
C. López González, D. Costa, C. Gómez, A. Varela, N. Villamor, D. Colomer,
M. Rozman, P. Abrisqueta, E. Montserrat, E. Campo, A. Carrió;
Hospital Clinic, Barcelona, Spain.
B-Cell chronic lymphocytic leukemia (B-CLL) is the most frequent
leukaemia in the Western world. This pathology is characterized by
the clonal expansion of morphologically mature small lymphocytes.
Convectional cytogenetics shows chromosomal abnormalities in 40-
50% of the cases, whereas FISH can detect about 80% of abnormalities.
The most common chromosomal abnormalities by FISH are del
13q14.3 in 50% of the cases, 20% trisomy 12 and less frequently deletions
of 11q22-23, 17p13 and 6q21. These alterations are associated
with clinical course; 17p13, 11q22-23 and del6q are linked with a
shorter survival, followed by trisomy 12 and the normal karyotype and
del 13q14.3 is associated with favorable clinical course.
From a single center, 171 samples with B-CLL have been analyzed using
conventional and molecular cytogenetics. Successful results have
been achieved in 90% of the cases by conventional cytogenetics and
94% by FISH. The rate of abnormality detections by conventional cytogenetics
was 53% (81/154) and 80% (129/161) by FISH. These rates
are in accordance with WHO. The results by molecular cytogenetics
were: 58% of the cases showed del 13q14.3, 22% had deletions of
11q22-23 and trisomy 12 and deletion of 17p13 had minor frequency,
17% and 14% respectively. However, 28% (43/154) of the cases had
alterations which had not been detected by FISH.
The study of CLL by conventional cytogenetics in all the samples will
be discussed to detect more abnormalities. This information will be
useful for the study of other mechanisms implicated in this pathology
and for the obtention of information for prognosis.
P06.186
cytogenetic studies among iranian patients with blood cancers
M. Khaleghian 1 , C. Azimi 2 , M. Khaleghian 2 , H. Kousari 2 ;
1 Tehran Medical Genetics Laboratory, Islamic Republic of Iran, 2 Department of
Genetics, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University
of Medical Sciences, Islamic Republic of Iran.
Cytogenetic studies are important diagnostic and prognostic factors
in evaluating patients with blood cancers. More than half of all leuke-
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