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

1991; Springer Nature; Volume: 63; Issue: 4 Linguagem: Inglês

10.1038/bjc.1991.133

1532-1827

Dhananjaya Saranath, SE Chang, LT Bhoite, Rekha G. Panchal, I B Kerr, AR Mehta, Newell W. Johnson, MG Deo,

RNA modifications and cancer

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.