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Epigenetics: a possible link between stress and melanocyte malignant transformation


Melanoma is the most aggressive skin cancer and highly resistant to currently available therapies. Like other types of cancer, melanoma is characterized by both genetic and epigenetic alterations. Epigenetic refers to heritable regulatory mechanisms of transcriptional activity that do not involve changes in DNA primary sequence. Epigenetic mechanisms comprise DNA methylation, histone modifications, chromatin remodeling and RNA associated silencing by microRNAs. Such mechanisms are essential to normal development and tissue-specific expression and their disruption could lead to inappropriate gene expression contributing to cancer development. In a different way of mutations, epigenetic mechanisms are potentially reversible and can change according to environment variation (nutrition, hormones, inflammation or any other environmental damage or insult). The onset of several pathologies, including cancer, has been associated with chronic stress conditions. Ultraviolet radiation and persistent inflammation, sustained stress conditions, are considered factors contributing to melanoma development. In this way, the comprehension of the relation among sustained stress, aberrant epigenetic marks and melanoma may clarify the initiation of this type of tumor and provide new avenues to develop novel therapeutic approaches and epigenetic markers for diagnosis and prognosis. In this review, we will discuss the current data on abnormal epigenetic marks in melanoma, available models to study this tumor type, and the potential role of epigenetic in mediating melanoma development by chronic insults. The promising of new epigenetic approaches in melanoma diagnosis, prognosis and treatment will be also commented. (AU)

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