Review Epigenetics of human melanoma: promises and challenges

Melanoma is the deadliest form of skin cancer with rising incidence and mortality rates. Although early-stage melanoma is highly curable, advanced-stage melanoma is refractory to treatment. This underscores the importance of prevention and early detection as well as the need to improve treatment and prognostication of human melanoma. Elucidating the underlying mechanisms of the initi-ation and progression of human melanoma can help identify potential targets of intervention for prevention, diagnosis, therapy, and prognosis of this disease. Aberrant DNA methylation and histone modifications are the best-established epigenetic mechanisms of carcinogenesis. The occurrence of epigenetic changes prior to clinical diagnosis of cancer and their reversibility through pharmaco-logic/genetic approaches offer a promising avenue for basic and translational research on human melanoma. Candidate gene(s) or genome-wide aberrant DNA methylation and histone modifications have been observed in human melanoma tumor tissues and cell lines, and correlated to cellular and functional characteristics and/or clinicopathological features of this malignancy. The present review summarizes the published researches on aberrant DNA methylation and histone modifications in connection with human mel-anoma.Representativestudiesarehighlighted toset forth thecurrentstateofknowledge,gaps in theknowledgebase, and futuredirec-tions in these epigenetic fields of research. Examples of epigenetic therapyapplied for humanmelanoma in vitro, and the challengesof its in vivo application for clinical treatment of solid tumors are discussed