p53 mutations in human bladder cancer.
Kusser-WC; Miao-X; Glickman-BW; Friedland-JM; Rothman-N; Hemstreet-GP; Mellot-J; Swan-DC; Schulte-PA; Hayes-RB
Environ Mol Mutagen 1994; 24(3):156-160
A study of the occurrence of p53 mutations in human bladder cancer was conducted. Thirty-eight bladder tissue specimens obtained at biopsy from 37 males who had been identified in screening tests as having possible bladder cancer were examined. The subjects completed a questionnaire to obtain information about smoking habits and previous bladder problems. Genomic DNA was extracted from the samples and analyzed for mutations in the p53 gene using the two stage polymerase chain (PCR) chain reaction and single strand configuration polymorphism analysis. All 37 subjects had a history of smoking; all but three smoked more than 20 pack years. Thirty- four subjects had bladder tumors, of which 32 were transitional cell carcinoma (TCC). The other two were in-situ TCCs. Twelve tumor specimens were graded as high grade tumors and 20 as low grade tumors. Tumors from the other two subjects could not be graded. Eight tumors had p53 mutations. The p53 mutations were detected in five high grade tumors and in three low grade tumors. The occurrence of these mutations in the tumors was not significantly associated with age or years of smoking. Analysis of specific mutations in p53 exons 5, 6, 7, 8, and 9 indicated that single transversions predominated accounting for 60% of the total. G/C to C/G transversions were the major type detected. Transitions and deletions accounted for 30 and 10% of the detected mutations, respectively. Two double mutations were also observed. No p53 mutations were found in tissue specimens from the three subjects without bladder cancer. The authors conclude that the study data confirm links between p53 mutations and advanced tumor grade, a high proportion of G/C to C/G transversions, and the occurrence of double mutations in human bladder cancer.
NIOSH-Publication; NIOSH-Author; NIOSH-Contract; Contract-211-91-0007; Bladder-cancer; Humans; Genetics; Mutagenesis; Molecular-biology; Cigarette-smoking; Nucleic-acids; Histopathology
Environmental and Molecular Mutagenesis