Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Weihrauch, M. et al.

Weihrauch, Benick, Lehner, Wittekind, Bader, Wrbitzk, Tannapfel,

High prevalence of K-ras-2 mutations in hepatocellular carcinomas in workers exposed to vinyl chloride.

OBJECTIVES: Vinyl chloride (VC) and its metabolites are human carcinogens associated with liver angiosarcomas (LAS) and also with hepatocellular carcinomas (HCCs). 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. The aim of the study was to evaluate possible specific K-ras-2 oncogene mutations in the case of HCCs due to VC. METHODS: The presence of K-ras-2 mutations was analysed in tissue from 12 patients with VC-associated HCCs. All patients had known long-term exposure to VC (average exposure amount: 9,942 ppm-years). Twenty patients with hepatocellular carcinoma due to hepatitis B (n = 7), hepatitis C (n = 5) and alcoholic liver cirrhosis (n= 8) served as a control group. The specific mutations were determined by direct sequencing of codons 12 and 13 of the K-ras-2 gene in carcinomatous and adjacent non-neoplastic liver tissue after microdissection. Immunohistochemical analysis was performed to detect p21ras protein. RESULTS: K-ras-2 mutations were found in five of 12 (42%) examined HCCs and in three cases of adjacent non-neoplastic liver tissue (25%). There were three guanine to adenine (G --> A) point mutations in the tumour tissue. All three mutations found in non-neoplastic liver from VC-exposed patients were also G --> A point mutations (codon 12- and codon 13-aspartate mutations). Within the control group, K-ras-2 mutations were found in three of 20 (15%) examined HCCs. CONCLUSIONS: Mutations of the K-ras-2 gene in hepatocellular carcinomas associated with VC exposure are frequent events. We observed a K-ras-2 mutation pattern characteristic of chloroethylene oxide, one of the carcinogenic metabolites of VC analysed in animal models. Our results suggest that VC had direct toxic effects not only on endothelial cells but also on hepatocytes, as it was previously only described in animal models.[1]

References

High prevalence of K-ras-2 mutations in hepatocellular carcinomas in workers exposed to vinyl chloride. Weihrauch, M., Benick, M., Lehner, G., Wittekind, M., Bader, M., Wrbitzk, R., Tannapfel, A. International archives of occupational and environmental health. (2001) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.