The incidence of p53 mutations increases with progression of head and neck cancer.

TLDR

The study aims to map the incidence and timing of p53 mutations during progression of head and neck squamous carcinoma. The authors sequenced conserved regions of the p53 gene in 102 lesions, including 65 primary invasive tumors and 37 noninvasive archival specimens (13 severe dysplasias and 24 carcinoma in situ). p53 mutations were present in 19 % of noninvasive lesions and rose to 43 % in invasive carcinomas, indicating that such mutations can precede invasion, with a mutation spectrum similar to lung squamous carcinoma and 64 % occurring at G nucleotides, suggesting a role for tobacco carcinogens.

Abstract

To establish a genetic model of the progression of head and neck squamous carcinoma we have defined the incidence and timing of p53 mutations in this type of cancer. We sequenced the conserved regions of the p53 gene in 102 head and neck squamous carcinoma lesions. These included 65 primary invasive carcinomas and 37 noninvasive archival specimens consisting of 13 severe dysplasias and 24 carcinoma in situ lesions. The incidence of p53 mutations in noninvasive lesions was 19% (7/37) and increased to 43% (28/65) in invasive carcinomas. These data suggest that p53 mutations can precede invasion in primary head and neck cancer. Furthermore, the spectrum of codon hotspots is similar to that seen in squamous carcinoma of the lung and 64% of mutations are at G nucleotides, implicating carcinogens from tobacco smoke in the etiology of head and neck squamous carcinoma.