Progress toward Isolation of a Breast Cancer Susceptibility Gene, BRCA1

The high incidence of breast cancer and/or ovarian cancer in some families appears to be due to germ-line mutations in BRCA1. Genetic analysis of such families suggests that the BRCA1 candidate region lies between D17S857 and D17S78 on chromosome 17q21 (Kelsell et al. 1993; Simard et al. 1993). To identify and isolate BRCA1, we have used linkage and meiotic recombination analysis, characterized regions displaying LOH in tumor DNA from BRCA1-linked families, performed YAC and cosmid clone isolation and ordering, and used three complementary transcript-searching strategies. We have identified as many as 28 genes from the BRCA1 candidate region, and we are searching for constitutive mutations in these candidate genes by several methods in an attempt to identify BRCA1.