title: Novel germline mutations of hMSH2 in a patient with hereditary nonpolyposis colorectal cancer (HNPCC) and in a patient with six primary cancers.
abstract: We screened for germline mutations of mismatch repair genes, hMLH1 and hMSH2, in five Japanese families carrying hereditary nonpolyposis colorectal cancer (HNPCC) and in a patient with multiple primary cancers. Screening the entire coding regions of both genes using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, we found two novel germline mutations in hMSH2. One was a 1-bp insertion in exon 12, detected in a patient who had undergone surgery six times for independent tumors (four primary colorectal carcinomas, a small intestinal carcinoma, and an endometrial cancer). The other, in a second patient, was a missense mutation from CTT to TTT at codon 390 in exon 7 that resulted in substitution of phenylalanine for leucine. This conservative alteration was not found in any of 50 normal controls, but we cannot exclude the possibility that it may represent a rare polymorphism rather than a factor in the disease.
authors.affiliation: Department of Medical Genetics, Osaka University Medical School, Suita, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Okamura
authors.forename: K
authors.initials: K
authors.lastname: Koyama
authors.forename: Y
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: M
authors.initials: M
authors.lastname: Monden
authors.forename: M
authors.initials: M
authors.lastname: Takami
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D018095:Germ-Line Mutation; D006801:Humans; D007078:Ileal Neoplasms / Q000235:genetics; D007414:Intestinal Neoplasms / Q000235:genetics*; D007564:Japan; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012004:Rectal Neoplasms / Q000235:genetics; D012811:Sigmoid Neoplasms / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein