Germ line mutations of hMSH2 and hMLH1 genes in Japanese families with hereditary nonpolyposis colorectal cancer (HNPCC): usefulness of DNA analysis for screening and diagnosis of HNPCC patients

✍ Scribed by M. Miyaki; M. Konishi; M. Muraoka; R. Kikuchi-Yanoshita; K. Tanaka; T. Iwama; T. Mori; M. Koike; K. Ushio; M. Chiba; S. Nomizu; J. Utsunomiya

• Publisher: Springer
• Year: 1995
• Tongue: English
• Weight: 848 KB
• Volume: 73
• Category: Article
• ISSN: 0946-2716
• DOI: 10.1007/bf00198903

✦ Synopsis

Mutations in hMSH2 and hMLH1 genes were analyzed in patients from 11 Japanese families that had been diagnosed as carrying hereditary nonpolyposis colorectal cancer (HNPCC) by clinical examination. Germ line mutations of hMSH2 gene were identified in 5 independent families in which colorectal (87% of patients), endometrial (30%), ovarian (17%), gastric (14%), and other cancers existed. Five mutations detected between codons 136 and 811 included single-base substitutions (C--)T and T--~G), a T deletion, and an A insertion, all of which produced stop codons resulting in truncated proteins, and an A---)T substitution at splice donor site of exon 5 which resulted in deletion of this exon. Moreover, one HNPCC family was presumed to have germ line mutation of hMSH2 gene because a somatic mutation of hMSH2 gene was detected in a cancer from a patient in this family. In addition to these 11 families already diagnosed with HNPCC, 3 new families with germ line mu-