2008 Barcelona - European Society of Human Genetics

Cancer genetics
mutations detected in hereditary breast cancer families . All together,
the mutation detection rate in BRCA1 or BRCA2 genes reached 39,8%
in hereditary breast cancer families (309 families carrying BRCA mutation
out of 778 analysed families with at least 2 diagnosed breast
and/or ovarian cancer cases before the age of 50) .
Any report about presence of BRCA1 mutation IVS5-12A>G in Slavic
population is missing in the BIC database . Therefore other methods
were tested for their capability to detect this mutation . We found that
HRM as well as DHPLC can perfectly detect the IVS5-12A>G mutation,
however detection with SSCP highly depends on running condition
. By using SSCP or HA the BRCA1 mutation IVS5-12A>G might
be easily overseen . Supported by the Ministry of Health of the Czech
Republic: Grant MZ0MOU2005
P04.038
Expression of BRcA1 and tP 53 genes in different types of
tumor
J. Ramic 1 , L. Kapur 1 , N. Lojo-Kadric 1 , D. Macic 1 , K. Radic 1 , N. Bilalovic 2 , K.
Bajrovic 1 ;
1 Institute for genetic engeneering and biotechnology, Sarajevo, Bosnia and
Herzegovina, 2 Department of pathology, University Clinical Center Sarajevo,
Bosnia and Herzegovina, Sarajevo, Bosnia and Herzegovina.
The TP53 is one of the main suppressors in many types of tumor ailments
. BRCA1 is another tumor suppressor gene involved in DNA
repair and it is best known by its role in the development and proliferation
of various types of breast and ovarian cancers . Previous studies
indicate that mutations in these genes are related to pathogenesis and
development of the disease .
Aim of our study was to determine if there is any relation between expressions
of these two genes and also to determine level of expression
of BRCA1 gene in colon cancer . Expression level of TP53 in different
cancers was compared to the expression of BRCA1 and beta -actin
that was used as a control gene . This study included samples from
76 subjects with breast, ovarian and colon cancer . Genetic material
was extracted from bioptic specimens retrieved from Department of
Pathology from University Clinical Center Sarajevo . Expression of the
observed genes was measured by real time PCR on Applied Biosystems
7300 device using SYBR green method .
P04.039
Contralateral prophylactic mastectomy in BRCA1/2 mutation
carriers with breast cancer
E. Dagan 1,2 , R. Gershoni-Baruch 1,3 ;
1 Rambam Health Care Campus, Institute of Human Genetics, Haifa, Israel,
2 University of Haifa, Department of Nursing, Haifa, Israel, 3 Technion-Institute of
Technology, The Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel.
The occurrence of bilateral breast cancer in BRCA1/2 mutation carriers
varies subject to factors such as age at diagnosis of 1 st tumor and
family history for breast-ovarian cancer . BRCA1/2 mutation carriers
are counseled to undergo prophylactic mastectomy (PM) and oophorectomy
(PO) . The incidence of contralateral prophylactic mastectomy
was evaluated in BRCA1/2 mutation carriers diagnosed with unilateral
breast cancer from one oncogenetic clinic in Northern Israel .
Socio-demographic and clinical profiles of 59 eligible BRCA1/2 mutation
carriers were collected . Women who opted for contralateral PM
were compared to those who choose medical surveillance .
Of the 59 women, three (5 .1%) underwent contralateral PM and 33
(55.9%) underwent PO and five (8.5%) had both contralateral PM and
PO . The three women who underwent contralateral PM were younger
than 40 years of age at diagnosis . Mean age at diagnosis was not statistically
different between those who opted for PM and those who preferred
surveillance . However, women who chose contralateral PM were
significantly younger than those who preferred follow-up (48.12±5.27
and 59 .81±9 .96, respectively, p=0 .001) . The only socio-demographic
variable found to be associated with PM was graduate level of education;
all eight women had academic education .
These findings suggest that most breast cancer patients diagnosed
with BRCA1/2 mutation declined PM. It is yet to be clarified whether
preferences of risk reduction management in Israel, are subject to
woman’s prevailing values or medical recommendations .
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P04.040
chromosomal damage after in vitro treatment with radiation or
mitomycin c in lymphocytes of BRCA /BRCA mutation carriers
S. Gutiérrez-Enríquez 1,2 , T. Ramón y Cajal 3 , C. Alonso 3 , A. Corral 4 , P. Carrasco
5 , J. Sanz 3 , C. López 3 , M. Ribas 5 , M. Baiget 2 , O. Diez 1,2 ;
1 Programa de Medicina Molecular i Genètica, Hospital de la Vall d’Hebron,
Barcelona, Spain, 2 Servei de Genètica, Hospital de la Santa Creu i Sant Pau,
Barcelona, Spain, 3 Servei d’Oncologia Mèdica, Hospital de la Santa Creu i Sant
Pau, Barcelona, Spain, 4 Grup de Mutagèsi, Universitat Autònoma de Barcelona,
Barcelona, Spain, 5 Servei de Radiofísica i Radioprotecció, Hospital de la
Santa Creu i Sant Pau, Barcelona, Spain.
INTRODUCTION AND OBJECTIVES: Mutations in BRCA1 and
BRCA2 account for a fraction of inherited susceptibility to breast (BC)
and ovarian cancer (OC) . The BRCA1/BRCA2 gene products help to
maintain genomic integrity after DNA damage . To investigate this capacity
in BRCA1/2 heterozygous cells, we have evaluated their in vitro
sensitivity to chromosomal damage induced by two mutagenic agents:
ionising radiation and mitomycin C (MMC) .
STUDY SUBJECTS AND METHODS: Lymphocyte cultures were
established from 20 BRCA1 mutation carriers (12 with cancer and 8
without), 21 BRCA2 mutation carriers (11 with cancer and 10 without)
and 11 non-carrier controls . The chromosomal damage (chromosome
breakage and chromosome loss) induced in vitro was assessed quantifying
bi-nucleated cells with micronuclei (MN) . MN can be used as
a measure of DNA repair capacity . Six cultures were set up for each
subject (2 treated with 2Gy gamma irradiation from Co-60, 2 treated
with 0,05 μg/ml of MMC and 2 without treatment).
RESULTS: The BRCA1/BRCA2 heterozygous lymphocytes did not
show a higher level of radiation-induced MN compared to the non-carrier
controls lymphocytes . In contrast, the BRCA2 lymphocytes, from
both women with and without cancer, presented higher levels of MN
after exposure to MMC than the lymphocytes of BRCA1 carriers and
women without mutation .
CONCLUSION: The haploinsufficiency of BRCA1/BRCA2 in peripheral
blood lymphocytes does not affect the repair of radioinduced DNA
lesions . But the absent of one BRCA2 functional allele is associated to
a higher level of chromosomal damage induced by MMC probably due
to an impaired DNA repair capacity .
P04.041
the prevalence of three mutations in BRcA genes in Romanian
women with familial breast cancer
D. Cimponeriu1 , P. Apostol1 , M. Toma1 , M. Stavarachi1 , D. Usurelu1 , D. Letitia1 ,
I. Radu1 , T. Burcos2 , E. Popa2 , I. Popa2 , S. Stanilescu2 , L. Gavrila1 ;
1 2 Institute of Genetics, Bucharest, Romania, Coltea Clinical Hospital, Bucharest,
Romania.
Background . BRCA1 and 2 mutations confer a substantial lifetime risk
to breast and ovarian cancer . The spectrum of mutation in these genes
has been not previously investigated in our country .
Aim . To evaluate the prevalence of BRCA1 and BRCA2 mutations in
women with demonstrated history of breast cancers .
Material and methods . We started this study in 2007 and selected 30
Caucasian patients with breast cancer which was confirmed by clinical
and paraclinical approach . All patients have at least one relative with
early breast cancer onset . Signed informed consent for all participants
was obtained before inclusion in study . We used blood samples to test
the presence of BRCA1 185 AG, BRCA1 5382 insC, BRCA2 6174 delT
mutations using commercial kit and classical PCR based methods . In
addition we screened by indirect methods a region of BRCA1 (1000
bp) for other mutations .
Results. We identified the heterozygous BRCA1 5382 insC mutation
in three patients, confirmed by both methods. The other two mutations
have been not detected . Thus, we consider that both methods
have similar efficiency in detection of these mutations. We also found
no mutations in investigated regions using indirect methods . Conclusion
. Our preliminary results showed that BRCA1 5382 insC could be
the most common mutation in Romanian women with familial breast
cancer .