Molecular characterization of germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in Taiwan

A total of 18 families with multiple cases of breast cancer were identified from southern Taiwan, and 5 of these families were found to carry cancer-a ssociated germline mutations in the BRCA1 and BRCA2 genes. One novel crypti c splicing mutation of the BRCA1 gene, found in two unrelated families, was shown to be a deletion of 10 bp near the branch site in intron 7. This mut ation causes an insertion of 59 nucleotides derived from intron 7 and resul ts in a frameshift, leading to premature translational termination of BRCA1 mRNA in exon 8. Deletions of 2670delC, 3073delT and 6696-7delTC in the BRC A2 gene were found in three other breast cancer families. All three deletio ns are predicted to generate frameshifts and to result in the premature ter mination of BRCA2 protein translation. Several genetic polymorphisms in bot h BRCA1 and BRCA2 genes were also detected in this investigation.