title: Activation of Ki-ras gene by point mutation in human liver angiosarcoma associated with vinyl chloride exposure.
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.
authors.affiliation: Hepatitis Research, Institut National de la Santé et de la Recherche Médicale, Lyon, France.
authors.forename: M J
authors.initials: MJ
authors.lastname: Marion
authors.forename: O
authors.initials: O
authors.lastname: Froment
authors.forename: C
authors.initials: C
authors.lastname: Trépo
mesh_terms: D001483:Base Sequence; D005602:France; D011905:Genes, ras; D006394:Hemangiosarcoma / Q000139:chemically induced / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009784:Occupational Diseases / Q000235:genetics; D015345:Oligonucleotide Probes; D009857:Oncogenes; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D013997:Time Factors; D014752:Vinyl Chloride / Q000633:toxicity*
chemical_list: D015345:Oligonucleotide Probes; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D014752:Vinyl Chloride