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 carcinogenes is, we analyzed 11 UV-induced murine skin cancers for mutations in the p53 tumor suppressor gene and found a 100% incidence rate. Such a hig h frequency of p53 mutations is unprecedented and suggests that this g ene plays an important role in the development of UV-induced skin canc ers. The mutations were predominantly ''UV-signature'' transitions (C --> T and CC --> TT) at pyrimidine-rich sequences located on the nontr anscribed strand of the gene. In addition, seven tumors harbored multi ple mutant alleles of p53, providing strong evidence for tumor heterog eneity at the molecular level.