title: RER phenotype and its associated mutations in familial gastric cancer.
abstract: To clarify the genetic background of gastric cancer, we collected 28 familial gastric cancers (FGCs) with reference to the Amsterdam criteria in hereditary non-polyposis colorectal cancer (HNPCC) and investigated the frequency of replication error (RER) at six microsatellite loci and frameshift mutations in its related genes in these tumors. RER was detected in seven (25%) of the 28 gastric cancers. Five (18%) cases showed RER at more than two loci. The apparent increased incidence of RER in FGC was not detected compared with that reported in sporadic gastric cancers previously. Among four cases with RER at more than three loci, frameshift mutations in the (A)8 track of the hMSH3 gene were detected in all the four cases and mutations in the (A)10 track of the transforming growth factor-beta type II receptor (TGF-beta RII) gene were detected in the three of them. Histologically, three of the four cases were of the intestinal type, and the other one was the diffuse type. No mutation was detected in the (C)8 and (GT)3 tracks of the hMSH6 and TGF-beta RII genes respectively. These results indicate that the acquisition of the RER phenotype equally influences the gastric carcinogenesis of both sporadic and familial cases, and that the majority of FGC is pathogenetically distinct from HNPCC.
authors.affiliation: Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shinmura
authors.forename: M
authors.initials: M
authors.lastname: Tani
authors.forename: J
authors.initials: J
authors.lastname: Isogaki
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Sugimura
authors.forename: J
authors.initials: J
authors.lastname: Yokota
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; C094443:G-T mismatch-binding protein; C078444:MSH3 protein, human; C421109:multidrug resistance-associated protein 1