TET proteins in cancer: Current ‘state of the art’

• Enzymes involved in DNA demethylation-TET play role in cell differentiation and carcinogenesis.
• Level of TETs and their products (oxidized 5-methylcytosines) is altered in many malignances.
• Increasing information is available regarding regulation of TET expression/activity in cancer.
• Readers of 5-mC derivatives need to be identified to estimate its role in cells.

Aberrations in DNA methylation patterns are observed from the early stages of carcinogenesis. However, the mechanisms that drive these changes remain elusive. The recent characterization of ten-eleven translocation (TET) enzymes as a source of newly modified cytosines (5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine) has shed new light on the DNA demethylation process. These cytosines are intermediates of an active DNA demethylation process and are epigenetic markers per se. In this review, we discuss the mechanism and function of TET proteins in biological processes as well as current knowledge regarding their expression and regulation in cancer.