BRCA1-Induced Ovarian Oncogenesis

Women carrying a germline mutation in BRCA1 have a 40% risk of developing ovarian cancer by the age of 70, and are also predisposed to cancers of the Fallopian tubes and breast (1). The molecular mechanisms responsible for cancer predisposition in these individuals remain unclear in spite of the huge effort focused on understanding the normal function of the BRCA1 protein since the encoding gene was first isolated. Particularly intriguing is the site specificity of the cancers that develop in such individuals. Indeed, although BRCA1 is expressed ubiquitously in most cell types, individuals carrying germline BRCA1 mutations are predisposed primarily to cancers of the breast and female reproductive tract. This chapter focuses on observations with an experimental model that not only provide a potential explanation why germline BRCA1 mutations are associated almost exclusively with predisposition to breast and ovarian cancers, but also sheds light into an underlying mechanism contributing to such predisposition.