[Show abstract][Hide abstract] ABSTRACT: We examined 21 ovarian and 24 breastovarian cancer families with BRCA1 mutations among a Japanese population. Twenty-four kinds of mutations were observed in these families. The DNAs of the mutation carriers (including the cancer patients) with these mutations were genotyped with microsatellite markers (D17S855,D17S1322,D17S1323 and D17S1325) located around the BRCA1 gene. The microsatellite genotyping showed that the alleles with the same mutations had the same haplotypes. This suggests that patients with the same mutation may have a common ancestor. On the other hand, a loss of heterozygosity (LOH) in the 4 microsatellite markers was observed in 48 (96.0%) of 50 tumor tissues examined. A combination of microsatellite genotyping and LOH analysis revealed that DNAs of the tumors retained the alleles with haplotypes common to the patients with the same mutation. Based on these results, we speculated on which mutations would occur in ovarian cancer families, working inversely from the haplotypes determined by this combination of methods. Consequently, T307A mutation in 2 families and C2919T in 4 families could be easily found. Applying these methods, we were able to detect haplotypes of 22 mutation alleles common to persons with the same mutations. Moreover, we employed LOH analysis and discovered two patients with a germline mutation of BRCA1 among 57 ovarian cancer patients without a family history of ovarian cancer. Determination of the retained haplotype by LOH analysis was proven to be an efficient tool to detect BRCA1 mutations from both familial and non-familial ovarian cancer patients.