Mutations in the conserved regions of p53 are infrequent in betel-associated oral cancers from Papua New Guinea.
Seventy-five % of the world's oral cancers arise in developing countries. In high incidence areas of Southeast Asia such as Papua New Guinea (PNG) the major region-specific risk exposure is betel quid chewing. While it has been shown that p53 gene mutations in the conserved midregion (exons 5-9) are a common feature of oral cancers in the developed world, there is no information on this type of genetic lesion in betel quid-associated oral cancers. We examined 50 oral squamous cell carcinomas, 20 from Baltimore, MD and 30 from PNG, for mutations in exons 5-9 of the p53 gene. DNA extracted from frozen biopsies was amplified by polymerase chain reaction, the purified product was sequenced directly, and mutations were confirmed by repeating the entire procedure. Mutations were found in 3 of 30 tumors from PNG (10%), whereas 9 mutations were detected among the 20 tumors (45%) from Baltimore, MD. This difference in frequency is statistically significant (P < 0.01) by chi 2 analysis. Nuclear accumulation of p53 protein, determined by immunohistochemistry with the CM-1 antiserum, was observed in the PNG cases harboring a missense mutation of the p53 gene. In agreement with the low number of PNG cancers with mutations, only 17% of the cases from PNG were immunostain positive. To explore whether less conserved regions of the gene are preferential targets for alterations in this patient group, sequence analysis in tumors from PNG was extended to outlying regions of the gene (all of exons 4 and 10, and splice sites), but mutations in only two additional tumors were identified. The presence of human papillomavirus DNA in PNG cases was examined with a polymerase chain reaction-based procedure, and viral sequences (human papillomavirus strains 11/16) were detected in two tumors. Human papillomavirus-triggered degradation of the tumor suppressor protein is thus unlikely to be a typical pathway to p53 dysfunction in tumors from PNG.
Thomas
S
S
Queensland Institute of Medical Research, Brisbane, Australia.
Brennan
J
J
Martel
G
G
Frazer
I
I
Montesano
R
R
Sidransky
D
D
Hollstein
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001114:Areca; D015142:Baltimore; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D010219:Papua New Guinea; D010946:Plants, Medicinal