Molecular analysis of BRCA1 and BRCA2 genes in Centre West Spanish population

Abstract

9572 Background: Inherited mutations in BRCA1 and BRCA2 genes predispose to breast and ovarian cancer. The proportion of high risk breast and breast/ovarian cancer families carrying BRCA1/2 germline mutations as well as the mutational spectra are variable and strongly dependant on the population and the types of families analyzed. Methods: DNA from 100 individuals with family history of breast/ovarian cancer was obtained and then analyzed by PCR, conformational sensitive gel electrophoresis (CSGE) and automated sequencing techniques. Results: We detected a total of 10 pathogenic mutations (5 for BRCA1 and 5 for BRCA2), 63 missense mutations (28 in BRCA1 and 35 in BRCA2) and 43 polymorphisms. The pathogenic mutations in BRCA1 were two deletions, 589delCT, 2031delG; one nonsense mutation in two unrelated families, C1806T (Q563X) and one missense mutation C5242A (A1708E). The pathogenic mutations in BRCA2 were two deletion, 8873delACCA and 3036delACAA in three unrelated families and one nonsense mutation C2604A (Y792X). 8873delACCA and Y792X mutations have not been previously described and Q563X mutation has not been previously described in Spanish population. The missense mutation H1284R in BRCA1 and H150R, D244N, W395G, K1057R, I2840V in BRCA2 and the polymorphism I785I and T2542T in BRCA2 have not been reported previously. Conclusions: Some variants of the genes appear to be unique to the population studied. The 3036delACAA mutation in BRCA2 gene is the most common in our studied population, the same as in Spanish population. The occurrence in Latin America of founder mutations that originated in Spain will be useful in establishing a cost-effective mutational analysis in such populations. No significant financial relationships to disclose.