2009 Vienna - European Society of Human Genetics

Cancer genetics
variant allele was taken into account, five polymorphisms emerged as
primary predictors for all OSCC stages: TIMP-2 (OR=26.33), TNF-α
(OR=15.27), IL-6 (OR=8.33), IL-8 (OR=3.54) and IL-10 (OR=2.65).
The contribution of these five factors in the occurrence of OSCC is
highly significant. Three of them increase risk more than tobacco (8-26
times versus 6 times, respectively). Based on these findings, possible
interactive mechanisms of implicated factors leading to OSCC development
and an algorithm of risk estimation will be presented.
P06.067
COX-2 −765 G > C functional promoter polymorphism and its
association with Oral squamous cell carcinoma.
L. Addala1 , K. CH2 , S. MD1 , K. Jamil2 ;
1 2 Institute of genetics and hospital for genetic diseases, Hyderabad, India, Indo
American Cancer Institute and Research Centre, Hyderabad, India.
Cyclooxygenase-2 (Cox-2) is a key enzyme in the conversion of arachidonic
acid to prostaglandins that has been shown to have a particular
importance in the progression of several malignancies including
OSCC. In the current report, we designed a case-controlled study to
evaluate the susceptibility and prognostic implications of the functional
−765 G > C genetic variation in OSCC patients. A PCR and restriction
fragment length polymorphism analysis was used to determine
the polymorphism in Indian population of patients with OSCC (n = 120)
and in healthy control subjects (n = 100). Genotype frequencies of
Cox-2 G765G, G765C and C765C were 77.5%, 15.83% and 6.66% in
the cancer patients and 91%, 7% and 2% in the controls, respectively.
Cox-2 G765C genotype is significantly associated (p-value = 0.04)
with OSCC patients when compared with controls. G765C genotype
was a 1.48-fold increased risk for OSCC. G765C genotype is statistically
significant with Chewing habitual risk factor (p=0.002). This is the
first report from India on the studies of COX-2 SNPs in Oral squamous
cell carcinomas and our data suggest that this genetic variant may play
a role in mediating susceptibility to OSCC cancer.
P06.068
Romanian ovarian cancer research for establishing a model of
tumors progression and metastasis evolution
N. Andreescu, M. Stoian, A. Belengeanu, D. Izvernariu, V. Belengeanu;
University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania.
In Romania, ovarian cancer is the second most frequent cause of death
among women consecutive to a malignancy. Due to the lack of clinical
simptoms, ovarian cancer is often discover in late stages and it is the
gynaecological malignancy with the worst prognosis. Another explanation
for this poor prognosis is the absence of screening tests which
would allow an early diagnose. Early diagnosis makes the difference
up to a 95 percent survival rate if the ovarian cancers are diagnosed in
an early stage and only 20 percent survival if the patients are in stage
III or IV. The genetic changes and molecular mechanism underlying
these tumors remain poorly understood. Department of Medical Genetics
of University of Medicine in Timisoara had initiated a research
program for ovarian cancer. In this study are included patients diagnosed
with ovarian tumors in the Western part of Romania. The study
implies DNA ploidy analysis using fluorescence in situ hybridization
(FISH) correlated with DNA copy number changes detected by comparative
genomic hybridization (CGH) and clinical outcome. The aim
is to develop a model for the progression of ovarian cancer by assessing
the tumor development and progression from the benign through
borderline to malignant ovarian tumors and identification of a genetic
profile associated with the cancer aggressiveness and metastasis.
P06.069
A significant loss of leucine rich repeat domain in a novel
candidate tumour suppressor gene PHLPP in cancer:
Expression studies
T. A. Tekiner 1 , F. Atalar 2 , A. Karabay-Korkmaz 1 , S. Anak 3 , U. Ozbek 4 ;
1 Istanbul Technical University, Molecular Biology and Genetics Department,
Istanbul, Turkey, 2 Istanbul University, Istanbul Medical Faculty, Child Health
Institute, Department of Pediatric Endocrinology, Istanbul, Turkey, 3 Istanbul
University, Istanbul Medical Faculty, Department of Pediatric Hematology and
Oncology, Istanbul, Turkey, 4 Istanbul University, Institute of Experimental Medical
Research (DETAE), Genetics Department, Istanbul, Turkey.
PTEN and a novel tumour suppressor, PHLPP are the negative regulators
of Akt signalling. In this study, the expression of four major func-
tional domains, PH domain, leucine-rich repeat region (LRR), PP2Clike
catalytic core and PDZ binding motif of PHLPP gene together with
PI3K/Akt pathway genes;Akt-1, PTEN and caspase-3 were examined
in pediatric Acute Myeloid Leukemia (pAML) patients.The expression
studies were performed by qRT-PCR in 35 pAML patients and in controls,
CD33+ blasts isolated from healthy bone marrows.The results
revealed that Akt-1 was up-regulated in pAML patients (p=0.06).PTEN,
PHLPP and caspase-3 were found to be decreased in pAML patients
compared to controls (3 times (p>0.05), 10 times (p>0.05) and 3 times
(p>0.05) respectively).Expression of PH , PP2C-like catalytic core and
PDZ binding domains were detected in our study group.Interestingly,
expression of LRR in pAML patients was not detected.Amplification
of PHLPP mRNA covering the region between exon 2 to exon 17 in
pAML samples lacking LRR expression resulted in three different transcript
variants.Direct sequencing results revealed a single nucleotide
change in exon 5 at position 55.PHLPP functional domain expressions
were also studied in various tumour tissues (colon, stomach, pancreas
and breast tumours).In tumour samples, LRR and PP2C-like catalytic
core expression were lost. PHLPP mRNA transcript variants different
than those observed in pAML samples were detected in tumour samples.Western
blot analysis results also confirmed the loss of non-truncated
PHLPP protein in pAML patients and tumour samples.It can be
proposed that PHLPP gene might act as a tumour suppressor in AML
leukomogenesis and tumorigenesis.
P06.070
impact of genetic polymorphisms on a training-induced
adaptation of the heart (the athlete’s heart)
R. Karlowatz 1 , J. Scharhag 2 , J. Rahnenführer 3 , J. Ernst 4 , W. Kindermann 5 , K.
Zang 1 ;
1 Institute of Human Genetics, University of Saarland/IGD Saar GmbH, Homburg/Saar,
Germany, 2 Centre for Sports Medicine, Outpatient Clinic University
Potsdam, Potsdam, Germany, 3 Fakultät Statistik, Technische Universität
Dortmund, Dortmund, Germany, 4 Department of Sports Medicine, Sportsclinic
Hellersen, Lüdenscheid, Germany, 5 Institute of Sports and Preventive Medicine,
University of Saarland, Saarbrücken, Germany.
Background: Athlete’s heart, an adaptation to long-time and intensive
endurance training, shows considerable individual differences. Genetic
polymorphisms in cardiologic relevant signalling pathways seem
to have an essential influence on the extent of physiological hypertrophy.
Objective: Analysis of polymorphisms in genes of the insulin-like growth
factor 1 (IGF1) signalling pathway and whose negative regulator myostatin
(MSTN), and the renin-angiotensin-aldosterone system (RAAS),
and their relation to left ventricular mass (LVM) of endurance athletes.
Methods: In 110 elite endurance athletes or athletes with a high
amount of endurance training (75 males and 35 females) and 27 controls,
which were examined by echocardiographic imaging methods
and ergometric exercise-testing, the genotypes of 16 polymorphisms
in 14 analysed genes were determined. Additionally, a mutation screen
of the MSTN gene was performed.
Results: The polymorphisms in the IGF1 and the IGF1R gene showed
a significant correlation to the LVM (IGF1: p=0.003; IGF1R: p=0.01).
The same applies to a so far unnoticed polymorphism in the MSTN
gene, whose mutation allele appears to increase the myostatic effect
(p=0.015). Contrary to a pathological hypertrophy, polymorphisms in
genes of the RAAS seem to have generally no significant influence on
a physiological hypertrophy. An important exception was a polymorphism
in the aldosterone synthase gene (CYP11B2 C-344T; p=0.02).
Moreover, combinations of some polymorphisms showed significant
synergistic effects on the LVM. Unexpectedly, these effects were only
detected in male athletes.
conclusions: We argue for the importance of selected polymorphisms
in these cardiologic relevant signalling pathways on the degree
of physiological hypertrophy of male athletes.
P06.071
Primitive neuroectodermal tumor (PNEt) located in third and
fourth ventricles and frontal lobe: case report of a 51-years-old
woman
V. Asmoniene 1 , D. Skiriute 1 , P. Vaitkiene 1 , I. Gudinaviciene 2 , S. Tamasauskas 3 ,
K. Skauminas 1,4 , V. P. Deltuva 1,5 , A. Tamasauskas 1,5 ;
1 Laboratory of Neuroscience, Institute for Biomedical Research, Kaunas, Lithu-