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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2001-4-5
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pubmed:abstractText |
Vinyl chloride (VC) is a know animal and human carcinogen associated with liver angiosarcomas (LAS) and hepatocellular carcinomas (HCC). In VC-associated LAS mutations of the K- ras -2 gene have been reported; however, no data about the prevalence of such mutations in VC associated HCCs are available. Recent data indicate K- ras -2 mutations induce P16 methylation accompanied by inactivation of the p16 gene. The presence of K- ras -2 mutations was analysed in tissue from 18 patients with VC associated HCCs. As a control group, 20 patients with hepatocellular carcinoma due to hepatitis B (n = 7), hepatitis C (n = 5) and alcoholic liver cirrhosis (n = 8) was used. The specific mutations were determined by direct sequencing of codon 12 and 13 of the K- ras -2 gene in carcinomatous and adjacent non-neoplastic liver tissue after microdissection. The status of p16 was evaluated by methylation-specific PCR (MSP), microsatellite analysis, DNA sequencing and immunohistochemical staining. All patients had a documented chronic quantitated exposure to VC (average 8883 ppmy, average duration: 245 months). K- ras -2 mutations were found in 6 of 18 (33%) examined VC-associated HCCs and in 3 cases of adjacent non-neoplastic liver tissue. There were 3 G --> A point mutations in the tumour tissue. All 3 mutations found in non-neoplastic liver from VC-exposed patients were also G --> A point mutations (codon 12- and codon 13-aspartate mutations). Hypermethylation of the 5' CpG island of the p16 gene was found in 13 of 18 examined carcinomas (72%). Of 6 cancers with K- ras -2 mutations, 5 specimens also showed methylated p16. Within the control group, K- ras -2 mutation were found in 3 of 20 (15%) examined HCC. p16 methylation occurred in 11 out of 20 (55%) patients. K- ras -2 mutations and p16 methylation are frequent events in VC associated HCCs. We observed a K- ras -2 mutation pattern characteristic of chloroethylene oxide, a carcinogenic metabolite of VC. Our results strongly suggest that K- ras -2 mutations play an important role in the pathogenesis of VC-associated HCC.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11286481-10022320,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/11286481-9989830
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0007-0920
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2001 Cancer Research Campaign.
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
84
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
982-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:11286481-Adult,
pubmed-meshheading:11286481-Aged,
pubmed-meshheading:11286481-Aged, 80 and over,
pubmed-meshheading:11286481-Carcinogens,
pubmed-meshheading:11286481-Carcinoma, Hepatocellular,
pubmed-meshheading:11286481-CpG Islands,
pubmed-meshheading:11286481-Cyclin-Dependent Kinase Inhibitor p16,
pubmed-meshheading:11286481-DNA Methylation,
pubmed-meshheading:11286481-Genes, p16,
pubmed-meshheading:11286481-Genes, ras,
pubmed-meshheading:11286481-Humans,
pubmed-meshheading:11286481-Liver Neoplasms,
pubmed-meshheading:11286481-Male,
pubmed-meshheading:11286481-Middle Aged,
pubmed-meshheading:11286481-Occupational Diseases,
pubmed-meshheading:11286481-Point Mutation,
pubmed-meshheading:11286481-Vinyl Chloride
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pubmed:year |
2001
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pubmed:articleTitle |
Frequent k- ras -2 mutations and p16(INK4A)methylation in hepatocellular carcinomas in workers exposed to vinyl chloride.
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pubmed:affiliation |
Institute of Occupational and Environmental Medicine, University of Hannover, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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