Comprehensive Analysis of the DNA Methylome of Human Cutaneous Melanoma

Novel screening techniques are allowing the depiction of the portraits of molecular alterations across cancer types, enabling a better understanding of the progression mechanisms and providing new therapeutic targets. Here, we performed an unbiased genome-wide DNA methylation analysis to interrogate the epigenetic events characterizing melanoma progression and prognosis, on a discovery cohort of clinical specimens. Our data underscores the importance of epigenetic regulation in triggering metastatic dissemination through the inactivation of central cancer-related pathways. Inactivation of cell-adhesion and differentiation programs unleashes malignant dissemination, and subsequent activation of inflammatory and immune system programs impairs anti-tumoral defense pathways. Moreover, we identify several markers of tumor progression previously unrelated with melanoma, and determined a survival prognostic signature with potential clinical applicability. All findings were validated in independent clinical cohorts and cross-correlated with publicly available databases, highlighting the relevance of the identified DNA methylation alterations for melanoma progression. Three different cancer types Nevi, metastatic melanoma, primary melanoma