RESUMEN
The aim of the present study was to analyze BRCA1 and BRCA2 mutations in Uruguayan families with breast and breast/ovarian cancer. Probands from 42 families with at least three cases of female breast cancer (BC) or two cases and subcriteria (paternal transmission, ovarian cancer, bilateral BC, male BC, Ashkenazi Jewish ancestry) in the same lineage, at least one diagnosed before age 50, were screened for germline mutations. PCR amplification of all exons and intron-exon boundaries were performed, followed by protein truncation test, heteroduplex analysis, and direct sequencing. We identified seven different truncating mutations in seven families, five in BRCA2 (three in site-specific BC families and two in breast-ovarian cancer families) and two in BRCA1 (one in a site-specific BC family and the other in a breast-ovarian cancer family). Both BRCA1 mutations (5583insT and 2687T>G) and one of the five BRCA2 mutations (3829insTdel35) were not previously reported. We also detected ten sequence variants of unknown significance, five of them not described before. The low frequency of BRCA1/2 mutations (0.17) is in agreement with that reported in studies which included families with similar selection criteria. However, the observed predominance of BRCA2 (0.12) over BRCA1 mutations (0.05) is in contrast with the higher proportion of BRCA1 mutations communicated for most previous studies, even those with a predominance of site-specific BC families. Meanwhile, it has been described in one Chilean and some Spanish and Italian reports, highlighting the strong dependence between the mutational spectra and the ethnicity of the population analyzed.