A NEW BRCA1 MUTATION IN A FILIPINO WOMAN WITH A FAMILY HISTORY OF BREAST AND OVARIAN-CANCER

Mutation of the BRCA1 gene in well-defined breast cancer families has been associated with an 87% lifetime risk for breast cancer and a 44% risk for ovarian cancer. Recent data indicate that the risk associated with these mutations is considerably lower, although still far greate r than the risk for disease in the rest of the population. Approximate ly 81% of the mutations that have been identified have been frameshift (71%) or nonsense (10%) mutations, and either may result in a truncat ed protein. The protein truncation test (PTT) is often used to screen patients at high risk, because sequencing of this large (100 kb) gene with its 22 coding exons is an arduous task. The PTT was used to analy ze genomic DNA and RNA from the peripheral blood of a 31-year-old Fili pino woman with a poorly differentiated, stage 2A breast carcinoma and a family history of breast-ovarian cancer. PTT identified the wild-ty pe protein fragment and an additional truncated protein fragment in th e patient's sample. Subsequent direct sequencing of the appropriate co ding region revealed a point mutation in exon 11 at nucleotide 2178, r esulting in a C > T transition that caused a termination (stop codon) in amino acid 687. To our knowledge, this is the first report of mutat ion of the BRCA1 gene in a Filipino family, and this in-frame stop-cod on mutation has not been reported previously.