Naslov
Sequence variants in BRCA1 and BRCA2 genes detected by high-resolution melting analysis as a tool in molecular genetic analysis of inherited breast cancers

Autori
Levanat, Sonja ; Levačić Cvok, Mirela ; Musani, Vesna ; Čretnik, Maja ; Ozretić, Petar

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
EJC Supplements / Elsevier - Amsterdam : Elsevier, 2009, 315-315

Skup
ECCO 15(European Cancer Organisation) and 34th ESMO (European Society for Medical Oncology) Meeting

Mjesto i datum
Berlin, Njemačka, 20.09.2009. - 24.09.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
BRCA1; BRCA 2 genes; breast cancer

Sažetak
Background The majority of cancers are result of somatic mutations ; but, epidemiological data indicates that 5-10% is hereditary, of which at least a third are associated with inherited mutations in the autosomal dominant tumor suppressor susceptibility genes BRCA1 and BRCA2. Their main contribution to tumorigenesis is inactivation of the second allele and consequently nonfunctional tumor suppression, which would be an early event in the oncogenic pathway of breast cancer. Carriers of BRCA1 and BRCA2 are at higher risk for developing of breast cancer by age 70 (between 45-85%) and of ovarian cancer (between 11-62%) ; carriers of mutation in one of those genes are also at increased risk for other cancers: uterine, cervical, pancreatic, gallbladder, bile duct, stomach cancers and melanoma. Therefore, screening for variants in the BRCA1 and BRCA2 genes can contribute to prevention and early cancer detection in cases with familial predisposition. Materials and methods Several screening methods are accepted by Eurogentest, and one of latest is based on high-resolution melting approach, that is efficient for rapid detection of sequence variants in cancer patients and their family members. This approach is based on differences in melting curves caused by variations in nucleotide sequence, but detected variants have to be confirmed by direct sequencing. Our lab established procedures for genetic analyses of those genes in families with high frequencies of breast/ovarian cancer in concordance with EMQN best practice guidelines for molecular genetic analysis in hereditary breast/ovarian cancer accepted at the EMQN workshop 2007. Results First screening was performed on elderly women with no personal or familial history of cancer, in order to identify benign high frequency variants of BRCA1 and BRCA2 in Croatian population. We found 21 different polymorphisms of BRCA1 and 36 of BRCA2 gene as normal variants in 200 BRCA1 and BRCA2 samples of healthy volunteers. We also tested the application of this approach using 25 coded samples with known mutations. Conclusions This is the first big screening study performed in this region, and it will contribute to further understanding of breast cancer and formation of the hereditary breast cancer registry in Croatia. Intention of this pilot project was to introduce genetic testing into the national program of early detection of breast and ovarian cancer. In Croatian population of 4.5 million, an average of 2, 200 new breast cancer and 400 ovarian cancer cases annually have been reported over the last ten years (with a moderate tendency of increase), and 800 women die of breast cancer each year (data from Central Bureau of Statistics of Republic of Croatia and Croatian National Institute of Public Health, 2006).

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA