PTCH mutations in squamous cell carcinoma of the skin

Ultraviolet light exposure is the major risk factor for the development of squamous cell carcinoma in Caucasians, Mutations in the tumor suppressor ge ne p53 have been identified in both squamous cell carcinomas and basal cell carcinomas. The human homolog of the Drosophila patched gene, has been sho wn to be mutated in sporadic basal cell carcinomas; however, mutations in t he patched gene have not been found in squamous cell carcinoma. In this stu dy, we screened a total of 20 squamous cell carcinoma samples for mutations in the patched gene, Using polymerase chain reaction-single strand conform ation polymorphism as an initial screening method, we identified one non-se nse mutation, two mis-sense mutations and three silent mutations in five sq uamous cell carcinoma samples. In one squamous cell carcinoma sample, we id entified a tandem GG-->AA transitional change at nucleotide 3152 in exon 18 of the patched gene that resulted in a premature stop codon at codon 1051, The three squamous cell carcinoma samples containing non-sense and mis-sen se mutations were isolated from individuals with histories of multiple basa l cell carcinoma. Sequence analysis of the p53 gene in these five squamous cell carcinoma samples identified one CC-->TT and three C-->T ultraviolet-s pecific nucleotide changes. Our study provides evidence that the patched ge ne is mutated in squamous cell carcinoma from individuals with a history of multiple basal cell carcinoma. The identification of ultraviolet-specific nucleotide changes in both tumor suppressor genes supports the notion that ultraviolet exposure plays an important part in the development of squamous cell carcinoma.