title: The role of hPMS1 and hPMS2 in predisposing to colorectal cancer.
abstract: Hereditary nonpolyposis colorectal cancer (HNPCC) is attributable to a deficiency of mismatch repair. Inactivation of DNA mismatch repair underlies the genesis of microsatellite instability in colorectal cancer. Germline mutations in three DNA mismatch repair genes, hMSH2, hMLH1, and hMSH6, have been found to segregate in HNPCC and HNPCC-like families. The two DNA mismatch repair genes hPMS1 and hPMS2 have also been suggested to predispose to HNPCC. In this study, 84 HNPCC and HNPCC-like kindreds without known mutations in the other three known DNA mismatch repair genes were screened for germline mutations in the hPMS1 or hPMS2 gene. No clear-cut pathogenic mutations were identified. Conversion technology was used to detect a large hMSH2 deletion in two affected members of the kindred in which the hPMS1 mutation was originally reported, whereas the hPMS1 mutation was only present in one of these two individuals. Since the hPMS1 and hPMS2 genes were first reported, germline mutations in hPMS2 have been demonstrated primarily in patients with Turcot's syndrome. However, no mutation in any of the two genes has been found to segregate in HNPCC families. Until there is better evidence for an increased colorectal cancer risk associated with germline mutations in these genes, a conservative interpretation of the role of mutations in these genes is advised.
authors.affiliation: Department of Molecular Medicine, Karolinska Institute, S-17176 Stockholm, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Yan
authors.forename: S
authors.initials: S
authors.lastname: Kuismanen
authors.forename: A
authors.initials: A
authors.lastname: Percesepe
authors.forename: M L
authors.initials: ML
authors.lastname: Bisgaard
authors.forename: M
authors.initials: M
authors.lastname: Pedroni
authors.forename: P
authors.initials: P
authors.lastname: Benatti
authors.forename: K W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: B
authors.initials: B
authors.lastname: Vogelstein
authors.forename: M
authors.initials: M
authors.lastname: Ponz de Leon
authors.forename: P
authors.initials: P
authors.lastname: Peltomäki
authors.forename: A
authors.initials: A
authors.lastname: Lindblom
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070956:MutL Proteins; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C088996:PMS1 protein, human; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070956:MutL Proteins; D045643:DNA Repair Enzymes