Mouse models of UV-induced melanoma: genetics, pathology, and clinical relevance

Melanocytes, a neural crest cell derivative, produce pigment to protect keratinocytes from ultraviolet radiation (UVR). Although melanocytic lesions such as nevi and cutaneous malignant melanomas are known to be associated with sun exposure, the role of UVR in oncogenesis is complex and has yet to be clearly elucidated. UVR appears to have a direct mutational role in inducing or promoting melanoma formation as well as an indirect role through microenvironmental changes. Recent advances in the modeling of human melanoma in animals have built platforms upon which prospective studies can begin to investigate these questions. This review will focus exclusively on genetically engineered mouse models of UVR-induced melanoma. The role that UVR has in mouse models depends on multiple factors, including the waveband, timing, and dose of UVR, as well as the nature of the oncogenic agent(s) driving melanomagenesis in the model. Work in the field has examined the role of neonatal and adult UVR, interactions between UVR and common melanoma oncogenes, the role of sunscreen in preventing melanoma, and the effect of UVR on immune function within the skin. Here we describe relevant mouse models and discuss how these models can best be translated to the study of human skin and cutaneous melanoma.