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

Cancer genetics
abilities to progress toward effective strategies of molecular diagnosis
and classification of glial tumors.
P0556. Study of genetic profile and intratumoral patterns of
clonal evolution in gliomas
A. L. Vital 1,2 , M. D. Tabernero 2 , I. Crespo 1,2 , O. Rebelo 3 , H. Tão 4 , F. Gomes 4 , M.
C. Lopes 1,5 , A. Orfao 2 ;
1 Center for Neuroscience and Cell Biology, University of Coimbra, Portugal,
2 Research Unit of University Hospital and Center for Cancer Research, University
of Salamanca, Spain, 3 Neuropathology Laboratory, Neurology Service,
University Hospital of Coimbra, Portugal, 4 Neurosurgery Service, University
Hospital of Coimbra, Portugal, 5 Faculty of Pharmacy, University of Coimbra,
Portugal.
Diffuse infiltrating gliomas are the most common tumors of the central
nervous system, being their clinical diagnosis based almost exclusively
on tissue histology, which relies mainly upon the World Health Organization
(WHO) classification scheme. However, a variable clinical
behavior is observed even in the same histological category and diagnostic
variability can occur due to the heterogeneous nature of these
tumors. So, the association between histologic and molecular classification
will be helpful to give prognostic and predictive information.
The main objective of our study is to identify molecular genetic alterations
that may account for the heterogeneity of gliomas, which will permit
to establish the genetic profile and patterns of clonal evolution in
individual patients. To correlate the chromosomal instability with the
gene expression profiles of these tumors, the tumor samples are firstly
studied by interphase fluorescence in situ hybridization (iFISH) analysis
and then submitted to c-DNA microarrays.
A total of 40 glioma patients were already analyzed. In all cases, iF-
ISH studies were performed on fresh tumor samples for the detection
of numerical/structural abnormalities for 10 loci in 8 different chromosomes
(1p36, 7q11, 7p11, 9q34, 9p21, 10q23, 13q14, 17p13, 19q13,
22q11). Among these 40 tumor samples, the mRNA from 20 samples
was already extracted and submitted to c-DNA microarray studies,
which are being performed.
Identification of homogeneous prognostic subgroups and definition of
clonal evolution patterns may be valuable for diagnosing and for predicting
prognosis and response to treatment in patients with glioma.
(Supported by a FCG project and FCT PhD fellowship, Portugal)
P0557. Surveillance of women at high risk of gynecological
cancers: Ten years results from one surveillance center
M. Pöyhönen 1,2 , T. Löppönen 3 , R. Winqvist 4 , J. Ignatius 4 , U. Puistola 5 ;
1 Department of Medical Genetics University of Helsinki, Helsinki, Finland,
2 Cancer Society of Finland, Helsinki, Finland, 3 Department of Child Neurology
Kuopio University Hospital, Kuopio, Finland, 4 Department of Clinical Genetics
University of Oulu, Oulu, Finland, 5 Department of Obstetrics & Gynecology
University of Oulu, Oulu, Finland.
Backround: Women at high risk of ovarian or endometrial cancers are
recommended to be under programmed surveillance once a year. The
efficacy of the screening has not been proven. The role of screening
instead of prophylactic surgery has been questionable.
Population and Screening: A cohort of 730 000 inhabitants in Northern
Finland was included in the study. 453 families contacted the Department
of Clinical Genetics. 137 women were classified as high risk for
gynaecological, breast or colorectal cancer and were taken for surveillance
program. The women with BRCA1 or BRCA2 mutation were
screened semiannually and other risk-groups annually with TVUS and
CA125 measurements. Mammography and Ultrasound or MRI was
performed once a year.
Results: Main indications for surveillance were: Family history of breast
and ovarian cancer: 39%; Breast cancer at young age: 19%; HNPCC
mutation: 20%; and BRCA1 or BRCA2 mutation: 14%.
Prophylactic surgery was performed on 16 women (12%): Eight
LH+BSO, six BSO and two mastectomies. 19 cancers and two premalignant
lesions were found: Seven breast cancer, two endometrial
cancers, one ovarian cancer, one endocervical cancer, five colorectal
cancers and three miscellaneous cancers (sarcoma, leukaemia, skin
cancer). 70% of the cancers were diagnosed during the first two years
surveillance period. 60% of the breast cancers and 80% of the colorectal
cancers were diagnosed in their advanced stage. Gynecological
cancers were diagnosed in their early stage.
Conclusion: In the screening and counselling program for women at
high risk in gynaecological cancers the role of prophylactic surgery
should be considered.
P0558. Real time quantification of human telomerase reverse
transcriptase mRNA in liver tissues from patients with
hepatocellular cancer and chronic viral hepatitis
M. Satra1 , N. Gatselis1 , D. Iliopoulos2 , D. Zacharoulis1 , G. N. Dalekos1 , A.
Tsezou1 ;
1 2 University of Thessaly, Larissa, Greece, The Ohio State University, Columbus,
OH, United States.
Telomerase activity (TA) and human telomerase reverse transcriptase
(hTERT) mRNA expression was determined, in liver tissues from patients
with hepatocellular carcinoma (HCC; n=13), chronic viral hepatitis
(CVH) B (n=19),C (n=13) and in 17 patients without liver disease
in whom liver biopsy was performed during cholecystectomy (control
group). TA was evaluated using TRAP assay and hTERT mRNA expression
was assessed using the LightCycler technology. TA was detected
in all HCC tissues compared to 15.6% of CVH (p