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

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 am...

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Bibliographic Details
Published in:British journal of cancer 1991-04, Vol.63 (4), p.573-578
Main Authors: SARANATH, D, CHANG, S. E, BHOITE, L. T, PANCHAL, R. G, KERR, I. B, MEHTA, A. R, JOHNSON, N. W, DEO, M. G
Format: Article
Language:English
Subjects:
Adult
Aged
Alleles
Base Sequence
Biological and medical sciences
carcinoma
Carcinoma, Squamous Cell - etiology
Carcinoma, Squamous Cell - genetics
Codon - genetics
DNA, Neoplasm - genetics
Female
Genes, ras - genetics
Glutamine - genetics
Glycine - genetics
Humans
Male
Medical sciences
Middle Aged
Molecular Sequence Data
Mouth Neoplasms - etiology
Mouth Neoplasms - genetics
Mutation
Oligonucleotide Probes
Plants, Toxic
Polymerase Chain Reaction
tobacco
Tobacco, Smokeless - adverse effects
Tobacco, tobacco smoking
Toxicology
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Summary: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.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.1991.133