2009 Vienna - European Society of Human Genetics

Cancer genetics
ania, 2 Department of Pathology, Kaunas Medical University Hospital, Kaunas,
Lithuania, 3 Kaunas University of Medicine, Kaunas, Lithuania, 4 Department of
Neurosurgery, Kaunas Medical University Hospital, Kaunas, Lithuania, 5 Department
of Neurosurgery, Kaunas University of Medicine, Kaunas, Lithuania.
Primitive neuroectodermal tumor (PNET) is rare but a highly malignant
tumor of the central nervous system. PNET is usually described as a
tumour of children being three fourths of these tumors appear in children
younger than 15 years, and 50% are seen in the first decade of
life. A second, smaller peak occurs in young adults (aged 21-40 years).
PNET is classified into two types, based on location in the body: peripheral
PNET and CNS PNET. It is a term for a group of small, round
cell tumors of the central and peripheral nervous system thought to be
derived from fetal neuroectodermal precursor cells.
We report on a 51-years-old woman with primitive neuroectodermal
tumor located in third and fourth ventricles and right frontal lobe. The
diagnosis was made in accordance with clinic, radiological and laboratory
investigations.
Immunohistochemically, tumor cells were immunoreactive for synaptophysin,
chromogranin A, some tumor cells immunoreactive for CD99.
There were no immunoreactive cells for GFAP and vimentin CK7.
CDKN2A homozygous deletion study: paired blood DNA and PNET tumor
tissue were investigated for CDKN2A deletion. We separately amplified
1α and 2 exons of p16(INK4a) tumor suppressor and exon 1β
of p14(ARF) for homozygous deletions. There were no homozygous
deletions observed neither for p16 (INK4a) nor for p14(ARF) tumor
suppressors studied.
All case review will be made in poster.
P06.072
cYP1B1 polymorphic variants associated with prostate cancer
risk in Bulgaria
R. Kaneva 1,2 , D. Kachakova 1 , A. Mitkova 1,2 , E. Popov 3 , A. Vlahova 4 , T. Dikov 4 ,
S. Christova 4 , I. Kremensky 5 , V. Mitev 1,2 , C. Slavov 3 ;
1 Molecular Medicine Center, Medical University - Sofia, Bulgaria, 2 Department
of Chemistry and Biochemistry, Medical University - Sofia, Bulgaria, 3 Department
of Urology, Alexandrovska University Hospital, Medical University - Sofia,
Bulgaria, 4 Department of Pathology, Alexandrovska University Hospital, Medical
University - Sofia, Bulgaria, 5 National Genetic Laboratory, University Hospital of
Obstetrics and Gynaecology, Medical Unversity - Sofia, Bulgaria.
Background: The CYP1B1 gene product is a member of the cytochrome
P450 enzymes involved in the androgen metabolism and one
of its tasks is catalysis of testosterone hydroxylation. Several studies
indicate that common polymorphic variants may increase the activity of
the enzyme and have a role in human prostate carcinogenesis.
Materials and methods: We have investigated the association with
prostate cancer (PC) risk of four polymorphisms in exons 2 and 3 of
CYP1B1 in a case-control study of 114 PC patients and 97 control individuals
with benign prostate hyperplasia and normal PSA level. The
polymorphisms were genotyped by direct sequencing.
Results: The strongest association with PC risk was demonstrated by
D449D, where the presence of either one (OR=1.4, 95% CI = 0.9-2.1;
p=0.052) or two C alleles (OR=1.8; 95% CI = 1.0-3.2; p=0.020) leads
to increased risk. The CC genotype occurred in higher frequency in patients
(50%) then in the controls (35%). Similarly in terms of L432V, the
frequent CC genotype (50% and 37% among patients and controls, respectively),
was associated with more than 1.5 fold PC risk (OR=1.69,
95% CI = 1.0-2.9; p=0.041). The polymorphisms N453S and A119S
did not show any significant association with PC risk.
Conclusions: Regarding the androgen metabolism at least several
studies have demonstrated the association between one or more genetic
variants of CYP1B1 gene and increased PC risk. It appears that
CYP1B1 polymorphisms D449D and L432V are associated with increased
PC risk in the Bulgarian population.
P06.073
Enhancement of the efficacy of Docetaxel with Conjugated
Linoleic Acid in LNcaP prostate cancer cells
S. Kakawand 1,2 ;
1 University of Aberdeen, United Kingdom, 2 Charles University, Czech Republic.
Prostate cancer is among the most commonly diagnosed cancers. The
use of chemotherapy in the treatment of prostate cancer has shown
promising results in improving the overall survival rate. The taxane
docetaxel (Taxotere) has proved efficaciously in controlling tumour
progression by interfering with microtubule dynamics. Currently drug
supplementation in cancer therapy has resulted in improved response,
by minimising its toxicity. The ω-6 fatty acid conjugated linoleic acid
(CLA) has raised interest as an effective tumouricidal agent without
inducing systemic harmful effects. The present study investigates
whether CLA supplementation would enhance the efficacy of docetaxel
in androgen sensitive LNCaP prostate cancer cells in vitro and
seeks possible genetic alterations in this process. LNCaP cells were
exposed to CLA followed by concurrent treatment with docetaxel for
24 and 48 hours. The cell viability was determined by MTT assay. Results
showed that higher concentrations of CLA enhance the efficacy
of docetaxel at 48 hour treatment time. Based on the involvement of
NF-κB mediated apoptosis, four genes of this pathway were selected.
From RT-PCR analysis, it was observed that CLA supplementation reduced
the expression of MAP2K4, MAX, AKT1 and FADD compared to
the effect of docetaxel on these genes. It is proposed that CLA supplementation
reduces the proliferatory activities of LNCaP cells possibly
by docetaxel-induced stress, resulting in the net antiproliferatory activities
of docetaxel not being opposed. The notion that supplementation
of chemotherapeutic drugs by fatty acids render cancerous cells to
undergo cell death more efficaciously, potentially sustains beneficial
prospects in cancer therapy.
P06.074
study of gene expression in prostate cancer samples
H. Savlı 1 , A. Szendroi 2 , R. Nagy 3 , I. Romics 2 , B. Nagy 3 ;
1 Medical Genetics Department & Clinical Research Unit, Kocaeli, Turkey,
2 Department of Urology, Semmelweis University, Budapest, Hungary, 3 Genetic
Laboratory, 1st Department of Obstetrics and Gynecology, Semmelweis University,
Budapest, Hungary.
We determind the changes in gene expression in PCA tissues and
to compare them to those in non-cancerous samples. Prostate tissue
samples were collected by needle biopsy from 21 PCA and 10 benign
prostate hyperplasic (BPH) patients. Total RNA was isolated, cDNA
was synthesized, and gene expression levels were determined by
microarray method (ABI, USA). In the progression to PCA, 738 upregulated
and 515 down-regulated genes were detected in samples.
Analysis using Ingenuity Pathway Analysis (IPA) software revealed
that 466 network and 423 functions-pathways eligible genes were
up-regulated, and 363 network and 342 functions-pathways eligible
genes were down-regulated. Up-regulated networks were identified
around IL-1beta and insulin-like growth factor-1 (IGF-1) genes. The
NFKB gene was centered around two up- and down-regulated networks.
Up-regulated canonical pathways were assigned and four of
them were evaluated in detail: acute phase response, hepatic fibrosis,
actin cytoskeleton, and coagulation pathways. Axonal guidance signaling
was the most significant down-regulated canonical pathway. Our
data provide not only networks between the genes for understanding
the biologic properties of PCA but also useful pathway maps for future
understanding of disease and the construction of new therapeutic targets.
P06.075
Epigenetic biomarker for the early diagnosis of prostate cancer
R. Dumache1 , M. Puiu1 , B. Bumbacila1 , G. Anton2 , N. Cucu3 ;
1University of Medicine and Pharmacy ‘’ Victor Babes’’, Timisoara, Romania,
2 3 National Institute of Virology, Bucharest, Romania, University of Bucharest,
Bucharest, Romania.
Aim: Prostate cancer is the commonest solid-organ malignancy diagnosed
in men, and represents the second cause of cancer related
death in men. In prostate cancer promoter hypermethylation of the
glutathione-S-transferase P1 (GSTP1) is the most frequent DNA alteration.
In our study we want to investigate the potential use of the GSTP1
gene hypermethylation as a biomarker for the early detection of prostate
cancer.
Materials and methods: For this study, we collected tissue and blood
samples from 29 patients with histologically confirmed prostate adenocarcinoma
and 24 patients with benign prostatic hyperplasia.
We performed methylation specific polymerase chain reaction (MSP)
for the promoter region of GSTP1 on the collected samples.
Results: By methylation specific polymerase chain reaction GSTP1
promoter hypermethylation was not found in blood and tissue samples