Frequency of BRCA1 dysfunction in ovarian cancer

Background: Ovarian cancer is one of the most common hereditary cancers in women. Mutations in the BRCA1 gene increase a woman’s risk of ovarian cancer. Testing for BRCA1 mutations is cumbersome and impractical for large populations. Therefore, we developed an efficient strategy to detect various types of BRCA1 dysfunction and also deter-mined the relative frequency of BRCA1 dysfunction in ovar-ian cancer. Methods: Tumors from 221 patients with epithe-lial ovarian cancer were screened for loss of heterozygosity (LOH) at the BRCA1 locus. BRCA1 complementary DNA (cDNA) and genomic DNA from all cancers with BRCA1 LOH (106 tumors) or noninformative status (15 tumors) were polymerase chain reaction (PCR) amplified and ana-lyzed for protein truncation in a coupled transcription/ translation test. When truncated BRCA1 protein was de