title: Missense mutation of the hMSH6 and p53 genes in sporadic urothelial transitional cell carcinoma.
abstract: Functional defects in DNA mismatch repair genes have been shown to be associated mainly with hereditary human malignancies. We examined genomic DNA from 88 sporadic transitional cell carcinomas (TCCs) of the urinary tract for mutations in hMSH6 gene by polymerase chain reaction and direct sequencing analysis. Mutational status of p53 gene was also studied as a potential target of genetic instability secondary to hMSH6 dysfunction. A total of 5 cases (5.7%: 5/88) displayed hMSH6 mutations all consisted of transition and located in exon 4, including three cases with missense mutation and two without change of corresponding amino acid. These three tumors with hMSH6 missense mutation had no microsatellite instability with five microsatellite markers tested. p53 gene mutations were detected in 22 cases (25.0%: 22/88). No tumors with p53 mutation had any hMSH6 missense mutations. Compared to the cases without hMSH6 alterations, the three patients with hMSH6 alterations had more frequent additional primary cancer (P<0.05). These findings provide the first in vivo evidence for the type of alterations and frequency of possible involvement of the hMSH6 mutations in sporadic type urothelial TCCs.
authors.affiliation: Department of Pathology II, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Furihata
authors.forename: T
authors.initials: T
authors.lastname: Shuin
authors.forename: T
authors.initials: T
authors.lastname: Takeuchi
authors.forename: H
authors.initials: H
authors.lastname: Sonobe
authors.forename: Y
authors.initials: Y
authors.lastname: Ohtsuki
authors.forename: Y
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Yuasa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins; D005260:Female; D005656:Fungal Proteins / Q000235:genetics*; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D029701:Saccharomyces cerevisiae Proteins; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C098790:MSH6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins