THE INCIDENCE OF P53 MUTATIONS INCREASES WITH PROGRESSION OF HEAD ANDNECK-CANCER

To establish a genetic model of the progression of head and neck squam ous carcinoma we have defined the incidence and timing of p53 mutation s in this type of cancer. We sequenced the conserved regions of the p5 3 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. T he incidence of p53 mutations in noninvasive lesions was 19% (7/37) an d increased to 43% (28/65) in invasive carcinomas. These data suggest that p53 mutations can precede invasion in primary head and neck cance r. Furthermore, the spectrum of codon hotspots is similar to that seen in squamous carcinoma of the lung and 64% of mutations are at G nucle otides, implicating carcinogens from tobacco smoke in the etiology of head and neck squamous carcinoma.