Genetic alterations in skin cancer.

Cancer is a multi-stage process in which the accumulation of genetic changes allows clonal expansion of abnormal cells that will eventually form a tumor. Skin cancer is the most common malignancy affecting human beings. Mutations of the tumor suppressor gene p53 are often found in non-melanoma skin cancer and pre-invasive lesions, like actinic keratosis. The type of mutations detected in the p53 gene strongly indicate UV light as the initiating and promoting agent in skin cancer development. Chromosome instability is also an early event in skin tumor formation. However, despite the huge amount of information available in the literature on molecular markers of skin cancers, much remains to be uncovered about the progression of genetic events that separate normal sun-exposed epidermis from skin cancer. In this paper the following issue will be addressed: how far are we from being able to define a human model for multistage skin carcinogenesis in humans?