Activation of Ki‐ras gene by point mutation in human liver angiosarcoma associated with vinyl chloride exposure

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Abstract
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.