Mutation testing of early-onset breast cancer genes BRCA1 and BRCA2

BRCA1 and BRCA2, genes predisposing to early-onset breast cancer, have been isolated and are characterized for mutation spectrum, risks of cancer, and function. The different methodologies to screen for mutations in BRCA1 and BRCA2 are briefly discussed including DNA-based methodologies and potential new assays. The numbers and types of mutations identified to date are described, including the problems of ascribing risk to missense mutations. Recurring, possibly founding mutations have been identified in several populations including Ashkenazi Jews, Icelanders, Swedes, and African Americans. From population-based studies, estimates are that 6%-10% of breast cancers are due to mutations in BRCA1 and BRCA2. Knowledge of mutation status raises additional questions including the interpretation of negative tests and the risks of breast and other cancers associated with positive test results.