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 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.
Saranath
D
D
Cell and Developmental Pathology Division, Cancer Research Institute, Bombay, India.
Chang
S E
SE
Bhoite
L T
LT
Panchal
R G
RG
Kerr
I B
IB
Mehta
A R
AR
Johnson
N W
NW
Deo
M G
MG
D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D003062:Codon / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D005973:Glutamine / Q000235:genetics; D005998:Glycine / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D015345:Oligonucleotide Probes; D010947:Plants, Toxic; D016133:Polymerase Chain Reaction; D014030:Tobacco, Smokeless / Q000009:adverse effects*
D003062:Codon; D004273:DNA, Neoplasm; D015345:Oligonucleotide Probes; D005973:Glutamine; D005998:Glycine