The p53 gene is mutated in numerous human cancers. We used it as a molecular target to characterize and try to understand the induction of mutations in human skin cancers. About 40-50% of all skin cancers in normal individuals and 60-80% of the DNA-repair-deficient xeroderma pigmentosum patients exhibit p53 mutations. Among these tumors, the melanomas are the less mutated ones. These mutations are characterized by specific signatures believed to be due to the UVB part of the solar spectrum. Different mutation spectra and different hot spots of mutations are found according to histopathological types of skin cancer. These data are interpreted in term of hot spots for DNA lesion induction, speed of local repair or sequence effects. The molecular analysis of these mutagenic characteristics should help us to understand the origin of human skin cancers in the general population.
