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Epigenetics of human melanoma： promises and challenges

Journal of Molecular cell Biology 2014年第5期8卷 356-367页

作者： Ahmad Besaratinia Stella Tommasi Department of Preventive Medicine Keck School of Medicine University of Southern California M/C 9603 Los Angeles CA 90033 USA

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 clinicopathologicai features of this malignancy. The present review summarizes the published researches on aberrant DNA methylation and histone modifications in connection with human melanoma. Representative studies are highlighted to set forth the current state of knowledge, gaps in the knowledgebase, and future directions in these epigenetic fields of research. Examples of epigenetic therapy applied for human melanoma in vitro, and the challenges of its in vivo application for clinical treatment of solid tumors are discussed.

关键词： aberrant DNA methylation epigenetic therapy histone modifications melanoma cell lines skin cancer

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