MUTATIONS IN THE BRCA1 GENE IN FAMILIES WITH EARLY-ONSET BREAST AND OVARIAN-CANCER

We analysed 50 probands with a family history of breast and/or ovarian cancer for germline mutations in the coding region of the BRCA1 candi date gene, using single-strand conformation polymorphism (SSCP) analys is on PCR-amplified genomic DNA. A total Of eight putative disease-cau sing alterations were identified: four of these are frameshifts and tw o are nonsense mutations. In addition, we found two missense mutations , one of which changes the final cysteine of the BRCA1 zinc finger mot if to glycine. These data are consistent with a tumour suppressor mode l, and support the notion that this candidate gene is in fact BRCA1. T he heterogeneity of mutations, coupled with the large size of the gene , indicates that clinical application of BRCA1 mutation testing will b e technically challenging.