BRCA1: the enigma of tissue-specific tumor development.

Recent evidence indicates that BRCA1, a gene product associated with breast and ovarian cancer susceptibility, is an important component of the cellular response to DNA damage. Despite being expressed ubiquitously in adult tissues, germline mutations in BRCA1 predispose individuals to breast and ovarian tumors with only minor effects on the predisposition to cancer in other sites. The reason for this tissue specificity of BRCA1 carcinomas must be found if we are to understand fully why these tumors occur and to enable us to design efficient preventive and therapeutic regimens. Here I propose that tissue-specific rates of loss of heterozygosity in the BRCA1 locus could contribute to tissue specificity in tumor development.