Acquired Secondary Events in the Pathogenesis of Mereditary Breast Cancer

摘要

Mutation of the BRCAl gene accounts for most families with an inherited predisposition to breast and ovarian cancer and many families with multiple cases of breast cancer only. The inheritance of a germline mutation of the BRCAl gene, although associated with a markedly increased incidence of breast cancer, is not solely responsible for the development of breast cancer in predisposed women and multiple other acquired steps appear to be required for the development of breast tumors in predisposed women. In this study we have identified over 50 women with BRCAl mutations for which tumor tissue is available for study. We present here acquired mutations in tumors from individuals who carry a predisposing mutation in BRCAl. We compare acquired mutations in a BRCAl associated tumor and a unique tumor cell line derived from this tumor. We compare and contrast acquired genetic abnormalities in tumors from two otherwise genetically identical siblings.