P53 mutational spectra are different between squamous-cell carcinomas of the lip and the oral cavity

We studied the P53 mutational spectra of 34 lip and 60 intra-oral squamous- cell carcinomas and examined possible etiological and prognostic correlatio ns for these tumor sites. For the P53 analysis of exons 5-8, we used PCR/TG GE screening followed by DNA sequencing. Mutations were found in 18/34 (53% ) lip and 22/60 (38%) intra-oral carcinomas. The p53 mutational spectrum of the intra-oral carcinomas comprised transitions and transversions in nearl y equal frequency (11 to 10), In comparison, transitions were 3.5 times mor e frequent than transversions (14 to 4) in carcinomas of the lip. The predo minant types of base change found in intra-oral tumors were G:C-to-T:A tran sversions and G:C-to-A:T transitions (32% each), while in lip tumors G:C-to -A:T transitions (70%) were the most frequent. The rate of lip tumors with mutations was higher in non-smokers (8/13) than in smokers (9/20). In contr ast, p53 mutations in intraoral tumors clustered in smokers (18/47 vs. 2/10 ), G:C-to-T:A transversions, regarded as tobacco smoke-associated in lung c ancer, were found in 2 moderate and 4 heavy smokers with intra-oral cancer. This base substitution was found in none of our lip cancers. In lip tumors , a high rate of mutations occurred at dipyridine sites (13/18); among thes e were 8 C-to-T transitions and 1 CC-to-TT tandem base transition. These ch anges are characteristic of DNA damage caused by UV light. The presence of mutational events at the DNA-binding surface of the p53 protein may correla te with poor clinical outcome. However, we could not find any statistically significant correlations between P53 status and survival. Only the recurre nce-free interval was significantly shortened in cases with mutations affec ting residues of the DNA-binding surface of the p53 protein, (C) 2000 Wiley -Liss, Inc.