p53 mutational spectra are different between squamous-cell carcinomas of the lip and the oral cavity

Abstract

We studied the p53 mutational spectra of 34 lip and 60 intra‐oral squamous‐cell carcinomas and examined possible etiological and prognostic correlations for these tumor sites. For the p53 analysis of exons 5–8, we used PCR/TGGE 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 nearly equal frequency (11 to 10). In comparison, transitions were 3.5 times more frequent than transversions (14 to 4) in carcinomas of the lip. The predominant types of base change found in intra‐oral tumors were G:C‐to‐T:A transversions 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 contrast, p53 mutations in intra‐oral tumors clustered in smokers (18/47 vs. 2/10). G:C‐to‐T:A transversions, regarded as tobacco smoke–associated in lung cancer, 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 these were 8 C‐to‐T transitions and 1 CC‐to‐TT tandem base transition. These changes are characteristic of DNA damage caused by UV light. The presence of mutational events at the DNA‐binding surface of the p53 protein may correlate with poor clinical outcome. However, we could not find any statistically significant correlations between p53 status and survival. Only the recurrence‐free interval was significantly shortened in cases with mutations affecting residues of the DNA‐binding surface of the p53 protein. Int. J. Cancer 88:82–86, 2000. © 2000 Wiley‐Liss, Inc.

Expression of p53 and its homologues in primary and recurrent squamous cell carcinomas of the head and neck

“…12,29 -31 The p53 mutation spectrum differs between squamous cell carcinoma of the lip and the oral cavity, indicating divergent exposure to carcinogenic agents. 32 We examined primary and recurrent squamous cell carcinomas from different locations of the head and neck and failed to observe site-specific mutation patterns when stratifying according to tumour location. Our mutation patterns of G:C3 T:A transversions in both primary and recurrent squamous cell carcinomas may indicate a carcinogenic effect of tobacco smoke in our patients.…”

Características sociodemográficas, clínicas e histopatológica de pacientes com carcinoma epidermóide de lábio: uma análise retrospectiva (1997-2004)

“…22 Estudos epidemiológicos verificam uma elevada frequência de indivíduos com lesões labiais submetidos a tal fator, 3,4,23 sendo este maior contato com os raios solares em virtude de atividades ocupacionais ao ar livre. 8,23 O elevado índice de radiação ultravioleta no Rio Grande do Norte 12 remete a uma maior preocupação para conhecer o perfil epidemiológico de enfermidades relacionadas a tal fator etiológico.…”

The Changing Aetiology of Oral Cancer and the Role of Novel Biomarkers to Aid in Early Diagnosis

“…A study of 94 oral squamous cell carcinomas (OSSC) found that 43% had TP53 mutations (Ostwald, 2000), similarly another study observed 48.66% of OSSC had p53 mutations (Hsieh, Wang et al 2001). An analysis of 18 oral tumours found 72% had TP53 mutation, however this high incidence may have been due to the small sample size (Partridge, 2000).…”

“…One investigation observed the highest number of mutations occurred in exon 7 and that the type of SNP was characteristic of lesion location. Lip lesions exhibited G:C to A:T transitions while intra-oral lesions exhibited an equal frequency of transitions and transversions (G:C to T:A) (Ostwald C, Gogacz P et al 2000). It has been proposed that these transversions are preferentially induced by breakdown products of benz[a]pyrenes, suggesting a strong correlation with tobacco usage (Ostwald C, Gogacz P et al 2000).…”

“…Lip lesions exhibited G:C to A:T transitions while intra-oral lesions exhibited an equal frequency of transitions and transversions (G:C to T:A) (Ostwald C, Gogacz P et al 2000). It has been proposed that these transversions are preferentially induced by breakdown products of benz[a]pyrenes, suggesting a strong correlation with tobacco usage (Ostwald C, Gogacz P et al 2000). A study of sequential epithelial dysplasias and squamous cell carcinomas suggested TP53 mutations correlated with an invasive tumour phenotype (Shahnavaz SA, Regezi JA et al 2000).…”