High frequency of p53 mutations in ultraviolet radiation-induced murine skin tumors: evidence for strand bias and tumor heterogeneity.

Exposure to UV radiation has long been associated with the development of skin cancers. To identify the molecular targets in UV carcinogenesis, we analyzed 11 UV-induced murine skin cancers for mutations in the p53 tumor suppressor gene and found a 100% incidence rate. Such a high frequency of p53 mutations is unprecedented and suggests that this gene plays an important role in the development of UV-induced skin cancers. The mutations were predominantly "UV-signature" transitions (C-->T and CC-->TT) at pyrimidine-rich sequences located on the nontranscribed strand of the gene. In addition, seven tumors harbored multiple mutant alleles of p53, providing strong evidence for tumor heterogeneity at the molecular level.