Mutation analysis of K-ras-2 in liver angiosarcoma and adjacent nonneoplastic liver tissue from patients occupationally exposed to vinyl chloride
Version of Record online: 19 JUL 2002
Copyright © 2002 Wiley-Liss, Inc.
Environmental and Molecular Mutagenesis
Volume 40, Issue 1, pages 36–40, 2002
How to Cite
Weihrauch, M., Bader, M., Lehnert, G., Koch, B., Wittekind, C., Wrbitzky, R. and Tannapfel, A. (2002), Mutation analysis of K-ras-2 in liver angiosarcoma and adjacent nonneoplastic liver tissue from patients occupationally exposed to vinyl chloride. Environ. Mol. Mutagen., 40: 36–40. doi: 10.1002/em.10084
- Issue online: 19 JUL 2002
- Version of Record online: 19 JUL 2002
- Manuscript Revised: 7 MAR 2002
- Manuscript Received: 30 JUL 2001
- liver angiosarcoma;
- vinyl chloride
Vinyl chloride (VC) is a potent liver carcinogen that induces angiosarcomas in humans and animals. Recent evidence shows that liver tumors from patients with VC exposure may have a specific K-ras mutation pattern. This study was performed to determine the status of K-ras-2 in liver angiosarcomas (LAS) from workers occupationally exposed to VC. We examined the presence of K-ras-2 mutations in 15 LAS from patients with known exposure to VC (median exposure: 8,260 ppm [range 3,900– 21,000 ppm]]. In all cases, other risk factors for the development of LAS were excluded. Direct DNA sequencing after microdissection of the tumor cells was used for the analysis. Heterozygous mutations of K-ras-2 were detected in 8/15 LAS (53%). Five patients (33%) had a mutation of codon 12 and three of codon 13 (20%). The most common changes were GA transitions in five LAS which lead to the substitution of aspartic acid for glycine in the resulting p21 protein. In two patients (13%), mutations of the K-ras-2 gene were identified in the adjacent nonneoplastic liver tissue. These data indicate that VC induces a high frequency of GA transitions in human LAS. This mutation pattern is likely a consequence of VC-DNA-adduct formation. Environ. Mol. Mutagen. 40:36–40, 2002. © 2002 Wiley-Liss, Inc.