Mutation analysis of the BRCA1 gene in Japanese patients with sporadic ovarian cancer

Background. Germline mutations in the BRCA1 gene, on chromosome 17q21, confer susceptibility to hereditary breast and ovarian cancer. It remains uncertain, however, whether somatic mutations in BRCA1 play a role in sporadic ovarian carcinogenesis. Methods. Samples of tumor and normal (peripheral blood) DNA were collected from 19 patients with sporadic (that is, no known family history) ovarian cancer. The BRCA1 gene alteration was analyzed for the entire coding region, using the single-strand conformation polymorphism (SSCP) technique followed by direct sequencing. Results. We found two somatic mutations in the 19 patients. One was an A deletion at nucleotide position 2073, leading to premature truncation of BRCA1 protein at codon 700, and the other was a G-to-A transition at nucleotide position 4498, resulting in substitution of serine for aspartic acid at codon 1460. In addition, loss of heterozygosity (LOH) was also observed at a BRCA1 intragenic marker in samples of both tumor and blood. Conclusion. Our data suggest that somatic mutation of the BRCA1 gene, in conjunction with LOH, may be a critical event in the genesis of a subgroup of sporadic ovarian cancer.