5-hydroxymethylcytosine in cancer: significance in diagnosis and therapy

Emerging data have demonstrated that 5-methylcytosine (5-mC) and its oxidized products 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxylcytosine (5-CaC) play unique roles in several biological processes, including the control of gene expression and in the pathogenesis of cancer. In this review, we focus on 5-hmC and the disruption of its distribution in several cancers, including hematological malignancies and solid tumors. We present an outline of how 5-hmC is closely associated with metabolic pathways and may be the missing link connecting epigenetics with metabolism in the context of cancer cells. Finally, we discuss the diagnostic and prognostic importance of 5-mC and 5-hmC patterning, and how we may be able to establish new paradigms in cancer therapy based on these alterations.