Direct and rapid detection of 5-hydroxymethylcytosine, a novel cancer hallmark in DNA, using electrochemical reaction

DNA cytosine methylation and its subsequent oxidation by ten-eleven translocation (TET) proteins to 5-hydroxymethylcytosine (5hmC) constitute a fundamental epigenetic modification in mammals. TET loss-of-function and the resulting reduction of 5hmC levels are recurrent in various cancers. Thus, the precise detection of 5hmC has great potential for early diagnosis and prognosis. Here, we show that 5hmC can be distinguished electrochemically, based on the inherent affinity of DNA bases to a gold surface. 5hmC-enriched DNA display less adsorption onto the gold surface, compared to those containing other cytosine analogs, and thereby, produce larger current response. We believe that this method will find broad application as a rapid, sensitive, and cost-effective biosensing technique for determining 5hmC levels in clinical samples, to expedite cancer diagnosis and prognosis evaluation.