The objective of this application is to obtain a better understanding of the molecular changes involved in the progression and the acquisition of the malignant phenotype in human melanoma, which remain largely unknown. To date, the majority of the efforts have conCentreated on studying the genetic changes leading to melanoma progression. However, epigenetic alterations, such as chromatin modifications, DNA methylation, and genomic imprinting are commonly found in cancer cells. Of particular relevance to this application are recent data indicating that RNA and RNA-regulated processes may hold an important role in melanoma progression. We have recently published in J Clin Invest that the RNA editing enzyme ADAR1 is lost in melanoma upon metastatic transition and it fundamentally regulates the proliferation of metastatic melanoma cells by controlling the biogenesis of microRNAs