Activation of Ki-ras gene by point mutation in human liver angiosarcoma associated with vinyl chloride exposure
✍ Scribed by Marie-Jeanne Marion; Olivier Froment; Christian Trépo
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- English
- Weight
- 478 KB
- Volume
- 4
- Category
- Article
- ISSN
- 0899-1987
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✦ Synopsis
Point mutations of c-ras genes were investigated in human angiosarcomas of the liver associated with occupational exposure to vinyl chloride. DNA prepared from either frozen or paraffin-embedded tissues was amplified by the polymerase chain reaction, and putative point mutations at codons 12, 13, and 61 of c-Ha-ras, c-Ki-ras, and N-ras were analyzed by dot-blot hybridization with allele-specific oligonucleotides. A G.C----A.T transition in the second nucleotide at codon 13 of the c-Ki-ras-2 gene was detected in 5 of 6 tumors. This mutation is likely a consequence of vinyl chloride-DNA adduct formation. It leads to the substitution of glycine by aspartic acid in the resulting p21 protein, a consistent amino acid substitution found so far in all types of human cancer exhibiting a codon 13-mutated Ki-ras gene.