hrvatski

Genetic testing for BRCA1 and BRCA2 germline mutations in Croatia. The value of testing unaffected members in families with breast/ovarian cancer

Purpose/Objective Epidemiological data indicates that 5‐15% of breast cancer and 10% of ovarian cancer cases are hereditary, and germline mutations in the tumor suppressor genes Breast Cancer Gene 1 (BRCA1) and Breast Cancer Gene 2 (BRCA2) account for the majority of hereditary breast and ovarian cancers. BRCA1 and BRCA2 are involved in a variety of cellular processes, including maintenance of genome stability, DNA repair via homologous recombination, transcriptional regulation, cell cycle control, chromatin remodeling and ubiquitinylation. Mutations are scattered throughout both genes and include disease‐causing mutations as well as unclassified variants. The purpose of this study was to estimate the incidence and spectrum of pathogenic mutations in BRCA1 and BRCA2 genes in high risk women in Croatia. Materials and Methods The screening was performed with high resolution melting analysis, direct sequencing and semi‐quantitative multiplex PCR method (Cvok et al. Clin Chem Lab Med 2008 ; 46(10):1376‐83). Protocols were certified by EMQN (European Molecular Genetics Quality Network) and provides high detection rate and complete coverage of BRCA1/2 genes. This study was funded by The Terry Fox Foundation. Candidates were volunteers from several national associations and support groups forKNJIGA SAŽETAKA / breast cancer patients, selected according to the set criteria. Results The complete coding sequences and exon‐intron boundaries analyses of both genes were carried out on 167 women with family history of breast and ovarian cancer. Nine pathogenic mutations in BRCA1 and five in BRCA2 gene were identified. Interestingly, 6 mutations in 7 family members who have not yet developed breast/ovarian cancer. Conclusion Benefit of BRCA1/2 mutation testing is clear, since mutations were detected in young unaffected women, who will be closely monitored for BreastCancer/OvarianCancer. Young unaffected family members are good candidates for mutation testing, since mutations can be detected at an early age, prior to cancer development. The value of testing enables prevention and early detection as well as application of new therapies specifically designed for BRCA mutation carriers.

tumori dojke; genetička istraživanja; dijagnostika

nije evidentirano