This proposal aims to address knowledge gaps concerning the causes and conditions that facilitate (FY15 Topic Area) melanoma initiation and relapse, which will aid in designing better strategies for (FY15 Focus Area) prevention and early treatment. Though melanoma is the most lethal form of skin cancer, the stimuli that cause melanoma initiation in melanoma prone skin are undefined. Also, the mechanisms promoting relapse have not been determined in tumors incorporating a system containing naturally occurring stromal and immune components. By identifying the mechanisms of melanoma initiation and relapse, and creating differential gene expression profiles capturing these processes, we will be able test prevention strategies with the candidate genes and model system defined by this proposal.