Towards a better understanding of the molecular mechanisms involved in sunlight-induced melanoma

Although much less prevalent than its nonmelanoma skin cancer counterparts, cutaneous malignant melanoma (CMM) is the most lethal human skin cancer. Epidemiological and biological studies have established a strong link between lifetime exposure to ultraviolet (UV) light, particularly sunburn in childhood, and the development of melanoma. However, the specific molecular targets of this environmental carcinogen are not known. Data obtained from genetic and molecular studies over the last few years have identified the INK4a/ARF locus as the "gatekeeper" melanoma suppressor, encoding two tumour suppressor proteins in human, p16^INK4a and p14^ARF. Recent developments in molecular biotechnology and research using laboratory animals have made a significant gene breakthrough identifying the components of the p16^INK4a/Rb pathway as the principal and rate-limiting targets of UV radiation actions in melanoma formation. This review summarizes the current knowledge of the molecular mechanisms involved in melanoma development and its relationship to sunlight UV radiation.