[HTML][HTML] Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma

CG Lian, Y Xu, C Ceol, F Wu, A Larson, K Dresser… - Cell, 2012 - cell.com
CG Lian, Y Xu, C Ceol, F Wu, A Larson, K Dresser, W Xu, L Tan, Y Hu, Q Zhan, C Lee, D Hu
Cell, 2012cell.com
DNA methylation at the 5 position of cytosine (5-mC) is a key epigenetic mark that is critical
for various biological and pathological processes. 5-mC can be converted to 5-
hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) family of DNA
hydroxylases. Here, we report that" loss of 5-hmC" is an epigenetic hallmark of melanoma,
with diagnostic and prognostic implications. Genome-wide mapping of 5-hmC reveals loss
of the 5-hmC landscape in the melanoma epigenome. We show that downregulation of …
Summary
DNA methylation at the 5 position of cytosine (5-mC) is a key epigenetic mark that is critical for various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) family of DNA hydroxylases. Here, we report that "loss of 5-hmC" is an epigenetic hallmark of melanoma, with diagnostic and prognostic implications. Genome-wide mapping of 5-hmC reveals loss of the 5-hmC landscape in the melanoma epigenome. We show that downregulation of isocitrate dehydrogenase 2 (IDH2) and TET family enzymes is likely one of the mechanisms underlying 5-hmC loss in melanoma. Rebuilding the 5-hmC landscape in melanoma cells by reintroducing active TET2 or IDH2 suppresses melanoma growth and increases tumor-free survival in animal models. Thus, our study reveals a critical function of 5-hmC in melanoma development and directly links the IDH and TET activity-dependent epigenetic pathway to 5-hmC-mediated suppression of melanoma progression, suggesting a new strategy for epigenetic cancer therapy.
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