title: hMSH2 mutations in hereditary nonpolyposis colorectal cancer kindreds.
abstract: It has recently been shown that hereditary nonpolyposis colorectal cancer (HNPCC) is caused by hereditable defects in DNA mismatch repair genes. However, the fraction of HNPCC due to defects in any one repair gene and the nature of these mutations are not known. We analyzed 29 HNPCC kindreds for mutations in the prototype DNA mismatch repair gene hMSH2 by a combination of linkage analysis, polymerase chain reaction-based screening, and sequencing of the coding region. The complete intron/exon structure of the gene was ascertained to facilitate this analysis. The results suggest that at least 40% of classic HNPCC kindreds are associated with germline mutations in hMSH2 and that most of these mutations produce drastic alterations in the predicted protein product.
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.forename: R E
authors.initials: RE
authors.lastname: Parsons
authors.forename: S R
authors.initials: SR
authors.lastname: Hamilton
authors.forename: G M
authors.initials: GM
authors.lastname: Petersen
authors.forename: H T
authors.initials: HT
authors.lastname: Lynch
authors.forename: P
authors.initials: P
authors.lastname: Watson
authors.forename: S
authors.initials: S
authors.lastname: Markowitz
authors.forename: J K
authors.initials: JK
authors.lastname: Willson
authors.forename: J
authors.initials: J
authors.lastname: Green
authors.forename: A
authors.initials: A
authors.lastname: de la Chapelle
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D015331:Cohort Studies; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005190:Family; D008040:Genetic Linkage; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*
chemical_list: D003062:Codon