Naslov
Germline BRCA1 and BRCA2 mutations in Croatian families with breast/ovarian cancer predisposition: Identification of three novel mutations

Autori
Musani, Vesna ; Levačić Cvok, Mirela ; Sušac, Ilona ; Sabol, Maja ; Ozretić, Petar ; Car, Diana ; Eljuga, Damir ; Levanat, Sonja

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

Izvornik
European Journal of Human Genetics / - , 2012, 162-162

Skup
European Human Genetics Conference

Mjesto i datum
Nürnberg, Njemačka, 23.06.2012. - 26.06.2012

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
BRCA1/2; breast/ovarian cancer; cancer predisposition

Sažetak
Breast cancer is the most common cancer in women after non-melanoma skin cancer, and it is the leading cause of cancer deaths in Croatia. Ovarian cancer is in the fifth place, both in incidence and mortality. About 5-10% of all breast and/or ovarian cancer cases are hereditary, and germline mutations in BRCA1 and BRCA2 account for the majority of hereditary breast and ovarian cancers. The contribution of BRCA1 and BRCA2 mutations to hereditary breast and ovarian cancer in Croatia is unknown. The purpose of this study was to estimate the incidence and spectrum of pathogenic mutations in BRCA1/2 genes in high risk women in Croatia. BRCA1/2 genes from 167 candidates (145 families) were scanned for mutations using High-resolution melting analysis (HRMA), direct sequencing and Quantitative multiplex PCR of short fluorescent fragments (QMPSF). We identified 14 pathogenic point mutations in 17 candidates, 9 in BRCA1 and 5 in BRCA2. Of those, 11 have been previously described and three were novel (c.5335C>T in BRCA1, and c.4139_4140dupTT and c.8175G>A in BRCA2). No large deletions or duplications involving BRCA1 and BRCA2 genes were identified. Two common BRCA1 sequence variants: c.2077G>A and c.4956G>A, were found more frequently in mutation carriers compared to healthy controls. In silico analyses identified one BRCA1 sequence variant (c.4039A>G) and two BRCA2 variants (c.5986G>A and c.6884G>C) as harmful with high probability and inconclusive results were obtained for one novel BRCA2 variant: c.3864_3866delTAA. Combination of QMPSF and HRMA methods provides high detection rate and complete coverage of BRCA1/2 genes.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA