Portraits of TET-mediated DNA hydroxymethylation in cancer

The discovery of TET-mediated DNA hydroxymethylation as a mechanism of DNA demethylation, along with the observation of disrupted hydroxymethylation patterns in cancer, sparked high hopes of better understanding malignant processes. In this review, we discuss a plethora of recent studies that have shed light on the mechanisms and biological consequences of DNA hydroxymethylation pattern changes in various cancers. A picture is taking shape, in which TET proteins appear as both promoters and suppressors of cancer. Their impairment at multiple levels creates abnormal 5hmC landscapes that affect, often in concert with key cancer pathways, a wider range of biological processes than initially proposed. As the picture gains in scope and precision, the prospect of 5hmC-pattern-targeting cancer therapies shimmers in the distance.