ABSTRACT
Shortly after the discovery of BRCA1, Stratton and colleagues localized and then isolated the second autosomal-dominant breast cancer susceptibility gene, BRCA2. BRCA2 was initially positioned in a 6 cM region on chromosome 13q12-q13 between the genetic markers D13S289 and D13S267. Using a set of Icelandic families, many of which included cases of male breast cancer, the interval in which BRCA2 lies was refined by microsatellite mapping to a 600 kb interval. Finally, using yeast artificial chromosomes and P1 artificial chromosomes, 14 overlapping clones were organized into a contig. To identify putative coding sequences, DNA from at least one affected member of 46 breast cancer families, which had shown linkage to BRCA2, was examined for sequence variants in candidate genes within the contig. Six different disease-associated mutations in BRCA2 were identified in these breast cancer families. As with the isolation of BRCA1, germline disease-associated mutations in BRCA2 were identified in a number of the breast cancer families tested. An association between BRCA2 germline mutations and male breast cancer was documented.
