The role of 5-hydroxymethylcytosine in melanoma

Malignant melanoma is a highly aggressive neoplasia of melanocytic origin. In part because of the lack of effective treatment methods, the incidence and mortality rates of this disease continue to increase. Rapidly accumulating evidence suggests that dysregulation of epigenetic mechanisms, including DNA methylation/demethylation, chromatin modification, and remodeling, and diverse activities of noncoding RNAs, play a central role in the pathogenesis of melanoma. The epigenetic mark 5-hydroxymethylcytosine (5-hmC) has attracted interest since 2009, when it was shown that ten-eleven translocation proteins can enzymatically convert 5-methylcytosine into 5-hmC, a key intermediate of DNA demethylation. Factors that regulate DNA hydroxymethylation are frequently altered in cancer, leading to deregulation of 5-hmC levels. In this review, we will discuss the relationship between melanoma and DNA hydroxymethylation, the regulation of DNA hydroxymethylation, and defects in this pathway in melanoma.