TRANSCRIPT IDENTIFICATION IN THE BRCA1 CANDIDATE REGION

Chromosome 17q12-21 is known to contain a gene (or genes) which confer s susceptibility to early-onset breast cancer and ovarian cancer (BRCA 1). Identification and isolation of BRCA1 will likely provide the basi s for increased understanding of the pathogenesis of breast and ovaria n cancer, the development of targeted diagnostic and therapeutic appro aches, and a means of screening women at risk of being BRCA1 mutation carriers. Genetic and physical maps of the BRCA1 candidate region have been largely completed and efforts are being directed at identificati on of candidate genes from within this region. We have begun the task of identifying transcripts from this region employing three complement ary strategies. These include: 1) direct cDNA screening with cosmids d erived from the BRCA1 region; 2) exon amplification; and 3) magnetic b ead capture. Transcripts identified using these approaches are being c haracterized for: 1) tissue expression pattern; 2) the presence of gen omic rearrangement in DNA derived from affected members of families be lieved to show linkage between breast cancer and genetic markers in th e BRCA1 candidate interval; 3) altered size and/or expression pattern in RNA prepared from such individuals; and 4) homology to known genes or functional motifs. Germline mutations in affected individuals from these families will serve as presumptive evidence of BRCA1 identity.