p53 Mutations in Human Head and Neck Cancer Cell Lines

Abstract

The p53 tumour suppressor gene is commonly mutated in human cancers. We performed a molecular analysis of the frequency and spectrum of p53 gene mutations in 40 cell lines (23 from oral cavity tumours and 17 from larynx tumours) derived from 33 patients with squamous cell carcinoma of the head and neck (SCCHN). Using PCR, SSCP, and sequence analysis, we detected the mutated p53 gene in 26 patients (79%); in 23 patients (70%) the wild-type allele of the p53 gene was deleted. Four patients had 2 p53 gene mutations each, and thus the total number ofp53 mutations observed was 30. Seven patients had 2 cell lines each, established from the primary and recurrent/metastatic tumour, and the status of the p53 gene (mutant or normal) was identical in both cell lines. Forty percent of the mutations were transitions, 33% transversions, and 27% deletions, insertions and other more complicated changes. In oral cavity tumours the predominant mutation type was G : C → A : T transition at a CpG site (50% of mutations), and in larynx tumours the predominant type was G : C → T : A transversion (50% of mutations). These suggest endogenous and exogenous factors in tumour etiology. The G : C → T: A transversions in larynx tumours are probably associated with mutagenic components in the cigarette smoke, but the causative factor in G : C → A : T transitions (apparent oxidative damage) remains to be identified.

Key Words:

• p53 tumour suppressor gene
• alterations
• SCCHN
• cell line