p53 gene mutations in asbestos associated cancers.
The accumulation of mutant p53 protein in cancer cells was observed by immunohistochemistry analysis. DNA was extracted from paraffin-embedded tissue. Exons 5, 7 and 8 were amplified and studied by PCR-SSCP and sequencing analysis. Ten cases of asbestos associated cancer tissue were studied, of which five cases had adenocarcinoma, and the other five had mesothelioma, squamous carcinoma, small cell lung cancer, adenosquamous carcinoma and malignant lymphoma respectively. Employing monoclonal antibody PAb1801, five cases were found to be mutant p53 protein positive. Seven cases were found to have mutations by PCR-SSCP. A total of 7 cases (8 mutations) were found to be positive and 4 cases were found to be positive by both of these analyses. Of the 8 mutations found by SSCP analysis, 4(50%, 4/8) were clustered in exon 8. A high mutation frequency was noticed in adenocarcinoma (80%, 4/5). Sequencing analysis on two specimens revealed two hotspot mutations. In codon 234, TAC for tyrosin was mutated to AAC for asparagine by a T to A transversion of the first letter. In codon 273, CGT for arginine was mutated to AGT for serine by a C to A transversion of the first letter. In conclusion, the mutation of p53 gene is common in asbestos associated cancers. However, the mutational spectrum of asbestos associated cancers might be different from that of non-asbestos associated cancers.
Liu
B C
BC
Institute of Occupational Medicine, Chinese Academy of Preventive Medicine, Beijing, China.
Fu
D C
DC
Miao
Q
Q
Wang
H H
HH
You
B R
BR
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics*; D000328:Adult; D000595:Amino Acid Sequence; D001194:Asbestos / Q000009:adverse effects*; D018196:Carcinoma, Adenosquamous / Q000139:chemically induced / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008223:Lymphoma / Q000139:chemically induced / Q000235:genetics*; D008654:Mesothelioma / Q000139:chemically induced / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation
D004273:DNA, Neoplasm; D001194:Asbestos