title: Genetic instability and mutation of the TGF-beta-receptor-II gene in ampullary carcinomas.
abstract: Ampullary carcinomas are relatively rare cancers of which very little is known in terms of carcinogenetic mechanisms at the molecular level. Genetic instability caused by mutations of mismatch-repair genes has been demonstrated to be responsible for hereditary non-polyposis colorectal cancers and a sub-set of sporadic colorectal cancers. In some of those tumors showing genetic instability, the transforming-growth-factor-beta(TGF-beta)-receptor-II gene has been found to be mutated in repetitive sequences and considered to be a target of replication error. We studied the role of genetic instability and associated TGF-beta-receptor-II-gene mutations in a series of 18 sporadic cases by analyzing 5 microsatellite loci (D2S123, D3S1029, D5S409, TP53 and BAT26) and by sequencing a poly-A repeat (nucleotides 709-718) in the TGF-beta-receptor-II gene. Microsatellite instability was observed in 4 (22.2%) and gene mutations in 14 (77.8%) cases. These data indicate that the TGF-beta-receptor-II gene might be a preferential target of genetic instability whose alteration might be specifically advantageous and constitute a common step in the development of ampullary carcinomas.
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Imai
authors.forename: N
authors.initials: N
authors.lastname: Tsurutani
authors.forename: H
authors.initials: H
authors.lastname: Oda
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Ishikawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II