High frequency mutation in codons 12 and 61 of H-ras oncogene in chewing tobacco-related human oral carcinoma in India

Br J Cancer. 1991 Apr;63(4):573-8. doi: 10.1038/bjc.1991.133.


57 primary tumour samples from Indian oral cancer patients with a 5-15 year tobacco chewing habit, were examined for mutational activation in codons 12, 13 and 61 of the H-ras, K-ras and N-ras oncogenes. The highly sensitive assay based on specific oligonucleotide hybridisation following in vitro amplification of unique sequences by polymerase chain reaction was employed. Mutations were detected in twenty (35%) of the samples and were restricted to H-ras, codons 12, 13 and 61. Two cases had concurrent mutations in codons 12 and 61. The majority of the mutations were at H-ras 61.2 (Glutamine to Arginine) and H-ras 12.2 (Glycine to Valine). Three of the less frequent mutations are apparently novel. Interestingly, eight of the samples with H-ras mutations also showed loss of wild-type H-ras, as judged by absence of signals for wild-type codons 12 or 61 on dot blots. The specific H-ras mutations in these oral malignancies associated with tobacco chewing, may represent an important example of an environmental carcinogen-induced step, in a pathway leading to malignant transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Base Sequence
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / genetics*
  • Codon / genetics
  • DNA, Neoplasm / genetics
  • Female
  • Genes, ras / genetics*
  • Glutamine / genetics
  • Glycine / genetics
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mouth Neoplasms / etiology
  • Mouth Neoplasms / genetics*
  • Mutation
  • Oligonucleotide Probes
  • Plants, Toxic*
  • Polymerase Chain Reaction
  • Tobacco, Smokeless / adverse effects*


  • Codon
  • DNA, Neoplasm
  • Oligonucleotide Probes
  • Glutamine
  • Glycine