p53 mutations at A:T base pairs in angiosarcomas of vinyl chloride-exposed factory workers.
Mutations in the p53 tumor suppressor gene are commonly found in the major human cancers and the mutational spectrum in some cancer types is consistent with the genotoxic effects of the associated environmental risk factors. Thus far there is little information on p53 mutations in cancers of factory workers with a history of carcinogen exposure in the workplace. Occupational exposure to vinyl chloride causes liver angiosarcomas (ASL) and also increases the risk of several other cancers. Loss of p53 function in osteo- and fibrosarcomas can occur by two different mechanisms, p53 mutation and amplification of the MDM2 gene. We examined tumors from five vinyl chloride-exposed patients, four with ASL and one with hepatocellular carcinoma (HCC), for evidence of MDM2 proto-oncogene amplification or p53 mutation in exons 5-8. Amplification of MDM2 was not found, but in two of the angiosarcomas an A:T to T:A missense mutation was detected. p53 sequence analysis of vinyl chloride associated cancers may provide valuable information on the relationship between carcinogen exposure and DNA damage in cancer-related genes.
Hollstein
M
M
IARC, Lyon, France.
Marion
M J
MJ
Lehman
T
T
Welsh
J
J
Harris
C C
CC
Martel-Planche
G
G
Kusters
I
I
Montesano
R
R
D000225:Adenine / Q000502:physiology; D000368:Aged; D001482:Base Composition; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics; D004247:DNA / Q000187:drug effects* / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005784:Gene Amplification / Q000187:drug effects / Q000235:genetics; D016158:Genes, p53 / Q000187:drug effects* / Q000235:genetics*; D006394:Hemangiosarcoma / Q000139:chemically induced* / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D009784:Occupational Diseases / Q000139:chemically induced* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D013936:Thymidine / Q000235:genetics; D014752:Vinyl Chloride / Q000009:adverse effects*
C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D004247:DNA; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D000225:Adenine; D013936:Thymidine; D014752:Vinyl Chloride