European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Cancer genetics
low: 8% (8/98 samples). Loss of heterozygosity (LOH) study with the
intragenic microsatellite marker D9S313 revealed LAMC3 locus deletions
in 8/48 (17%) breast cancer samples. Methylation and LOH
studies were also performed for bladder and clear cell renal cancers,
demonstrating higher frequencies of LAMC3 molecular alterations.
The study was supported in part by Applied Biosystems, USA.
Molecular pathology of the LAMC3 gene in breast, renal and bladder cancers
Total number of
samples tested
LOH
Number (%)of
hetero-zygotes
Number (%) of
samples with LOH
Methylation Expression
Breast cancer 58 48 (83%) 8 (17%) 8/98 (8%) 29/31 (94%)
Clear cell renal
cancer
75 49 (65%) 10 (20%) 8/34 (24%) n/a
Bladder cancer 77 45 (58%) 12 (27%) 13/45 (29%) n/a
P0570. Angiotensin Converting Enzyme (ACE) Insertion/Deletion
(I/D) Gene Polymorphisms in Leukemic Hematopoiesis
I. Akalin 1 , E. Koca 2 , H. G. Karabulut 1 , D. Cetiner 2 , I. C. Haznedaroglu 2 , M.
Hayran 3 , I. K. Onal 4 , O. I. Ozcebe 2 , A. Tukun 1 ;
1 Ankara University Faculty of Medicine, Department of Medical Genetics,
Ankara, Turkey, 2 Hacettepe University Medical School, Department of Internal
Medicine, Hematology Division, Ankara, Turkey, 3 Hacettepe University Medical
School, Department of Preventive Oncology, Ankara, Turkey, 4 Hacettepe University
Medical School, Department of Internal Medicine, Ankara, Turkey.
Renin angiotensin system (RAS) represents an autocrin/paracrin system
affecting normal and neoplastic hematopoiesis. In this study, we
investigated angiotensin converting enzyme (ACE) insertion/deletion
(I/D) gene polymorphisms, which may affect the behavior of the local
RAS in hematological neoplastic disorders.
Our results indicated alterations in the polymorphisms of major RAS
component, ACE in leukemic hematopoiesis. ACE ID/II genotype frequency
is increased in leukemic patients compared to the controls.
Disease risk in patients with insertion (ID or II) is increased (chisquared,
p=0.008, OR: 3.2[1.3-7.9]). ID/II genotype was found in 80.4
% of the patients while it was 55.9 % in the control group. Hence, our
study firstly provided evidence that the ACE ID/II gene polymorphism
may be linked to the development of leukemia as a clue of activated
local RAS in leukemogenesis.
Leukemias * ACE Gene Polymorphism Crosstabulation
ACE-Polymorphisms
DD ID/II TOTAL
Leukemia ALL Count 1 7 8
% within ALL 12,5% 87,5% 100,0%
% within ACE-pol 25,0% 22,6% 22,9%
AML Count 1 9 10
% within AML 10,0% 90,0% 100,0%
% within ACE-pol 25,0% 29,0% 28,6%
CML Count 2 15 17
% within CML 11,8% 88,2% 100,0%
% within ACE-pol 50,0% 48,4% 48,6%
Total Count 4 31 35
% within leukemias 11,4% 88,6% 100,0%
P0571. Molecular-genetic analyses of children with
hematological malignances in Bashkortostan Republic, Russia
E. Yakupova, T. Krasavtceva, R. Stepanova, R. Bayramgulov, V. Mahonin;
Children republic hospital, Ufa, Russian Federation.
Hematological malignances are the most common cancer in childhood.
Chromosome rearrangements determine the prognosis of diseases
and play an important role in the choice of treatment protocols, allowing
the control of minimal residual disease during and after treatment.
During the 2005-2006 years, 34 bone marrow samples of patients with
leukemia tested to the presence of chromosomal aberrations by the
method of reverse transcription-polymerase chain reaction.
1 1
We detected three patents with t(1;19) E2A/PBX among 26 ALL samples.
This translocation defines an unfavorable prognosis. Patients
with t(1;19) received high-risk treatment protocol, that permit to reach
molecular remission and decrease risk of relapses.
Among ALL patients - three were with t(12;21) TEL/AML1. This translocation
defines a favorable prognosis. Patients with t(12;21) received
standard-risk treatment protocol, that permit to reach molecular remission
and decreases the risk of complications.
Among ALL patients - one had a t(9;22) BCR/ABL p210. This translocation
defines a very unfavorable prognosis. This child has received
high-risk treatment protocol in combination with STI571 (Glivec) 400
mg daily.
Among 6 AML patents, one was with AML-M3, translocation t(15;17),
PML/RARA confirmed the diagnose. This patient has received AML-
APL protocol in combination with ATRA (Tretionin).
We detected t(9;22) BCR/ABL p210 translocation in two samples in
patients with chronic phase of CML. These patients have received
treatment with Glivec 400 mg daily. After 6 and 12 months of treatment
molecular remission was achieved, t(9;22) was not detected.
Thus, molecular-genetic analyses plays an important role in diagnostics,
choice of treatment and prediction of relapse in hematological
malignancies.
P0572. Cytogenetics, immunophenotype and biomolecular
parameters-particularities in acute lymphoblastic leukemia
M. Puiu, S. Arghirescu, M. Bataneant, R. Firescu, L. Stana, M. Baica, M. Mihailov,
M. Serban;
IIIrd Pediatric Clinic, Timisoara, Romania.
Background. Acute lymphoblastic leukemia (ALL) refers to a group of
heterogeneous diseases with different clinical expression and prognosis.
Therefore, patients require precise and complete initial evaluation
of risk factors including cytogenetics, immunophenotype and biomolecular
assessment in order to plan an individualised, optimal treatment
regimen.
Objectives. We aimed at evaluating the biological profile of leukemic
cells and its particularities in ALL.
Patients and methods. We analyzed cytogenetics, cell surface markers
and biomolecular parameters in connection with clinical parameters
(sex, age, risk factors, ethnic group, central nervous system leukemia,
mediastinal mass) in 156 ALL patients aged 0-18 years, treated in our
Clinic between 1990-2002.
Results. Compared to data from literature, in our study group we
noticed no differences between sex distribution (56% vs. 57% being
males), a lower proportion of patients belonging to 2-6 years age group
(53.8% vs. 77%) and a double proportion of patients older than 6 years
(41.6% vs. 20%). Frequency of medium and high risk forms was higher
in study group (75.6% and 10.2% vs. 59.46% and 10.65%) and also
the incidence of L3-ALL (3.3%). Biomolecular assessment revealed
a comparable proportion of patients with t(9,22)-BCR-ABL mutation
(1.28%) and a higher proportion of t(14,11) MLL-AF4 (2.56%). Leukemic
cells expressed lymphoid CD10 marker in 35.07% vs. 63.01%.
There were no differences between central nervous system involvement
in newly diagnosed ALL (3.8% vs. 4%). These data can explain
the worse prognosis of our patients.
Conclusions. Our results provide practical information that should be
taken into account for planning individualized treatment.
P0573. Molecular basis of the Li-Fraumeni syndrome (LFS): an
update from the French LFS cohort
G. Bougeard 1 , S. Baert-Desurmont 1 , C. Martin 1 , S. Vasseur 1 , L. Brugières 2 , B.
Bressac - de Paillerets 3 , A. Chompret 4 , D. Stoppa-Lyonnet 5 , C. Bonaïti-Pellé 6 ,
T. Frebourg 1 ;
1 Inserm U614 and Department of Genetics, Rouen University Hospital, Institute
for Biomedical Research, Rouen, France, 2 Department of Pediatric Oncology,
Institut Gustave Roussy, Villejuif, France, 3 Department of Genetics, Institut
Gustave Roussy, Villejuif, France, 4 Department of Medicine, Institut Gustave
Roussy, Villejuif, France, 5 Department of Genetics, Institut Curie, Paris, France,
6 Inserm U535, Villejuif, France.
The Li-Fraumeni syndrome represents one of the most devastating
genetic predispositions to cancers and is characterized by a wide
spectrum of early-onset malignancies (sarcoma, brain tumour, adrenocortical
tumour, breast cancer, leukemia, lymphoma, gastric carcinoma,
gonadal germ cell tumour, colorectal and lung cancer). We