MULTIPLE MUTATION SCREENING OF THE BRCA1 GENE IN 1000 JAPANESE BREASTCANCERS

To detect BRCA1 mutations in Japanese breast cancer patients, we scree ned 1,000 unselected primary cancers for mutations in exon 11, which a ccounts for 61% of the entire BRCA1 coding sequence. Using a method ba sed on multiples single-strand conformational polymorphism (SSCP) anal ysis of multiple restriction fragments generated by restriction-enzyme digestion of amplified DNA, we identified eight mutations. All eight were germline mutations; four of them were non-sense mutations or smal l deletions resulting in premature stop codons, and the other four wer e missense mutations. The Japanese carriers of these mutant BRCA1 alle les had developed breast cancers at ages ranging from 45 to 62, five o f them bilaterally.