title: Somatic mutations in the hMSH2 gene in microsatellite unstable colorectal carcinomas.
abstract: Microsatellite instability is frequently seen in tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC). Germline mutations in the mismatch repair gene hMSH2 account for approximately 50% of these cases. Tumors from sporadic cases also exhibit this microsatellite instability phenotype, although at a lower frequency, and very few somatically derived mutations have so far been reported in such tumors. In this study DNA from 23 primary colorectal carcinomas (four familial and 19 sporadic cases) exhibiting microsatellite instability were screened for mutations in the hMSH2 gene using constant denaturant gel electrophoresis (CDGE). Among the sporadic cases, five (26%) were found to have somatically derived mutations. One tumor revealed two different mutations, possibly leading to a homozygous inactivation of the gene. One of the four familial cases was classified as having HNPCC, and a germline as well as a somatic mutation were found in this tumor. These results demonstrate that a considerable proportion of sporadic colorectal cancers with microsatellite instability, have somatic mutations in the hMSH2 gene.
authors.affiliation: Department of Genetics, Norwegian Radium Hospital, Montebello, Oslo, Norway.
authors.forename: A L
authors.initials: AL
authors.lastname: Børresen
authors.forename: R A
authors.initials: RA
authors.lastname: Lothe
authors.forename: G I
authors.initials: GI
authors.lastname: Meling
authors.forename: S
authors.initials: S
authors.lastname: Lystad
authors.forename: P
authors.initials: P
authors.lastname: Morrison
authors.forename: J
authors.initials: J
authors.lastname: Lipford
authors.forename: M F
authors.initials: MF
authors.lastname: Kane
authors.forename: T O
authors.initials: TO
authors.lastname: Rognum
authors.forename: R D
authors.initials: RD
authors.lastname: Kolodner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics*; D004276:DNA, Satellite / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005656:Fungal Proteins; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein; D009154:Mutation; D011110:Polymorphism, Genetic
chemical_list: D004273:DNA, Neoplasm; D004276:DNA, Satellite; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D051718:MutS Homolog 2 Protein