1. Loss of 5-Hydroxymethylcytosine Is an Epigenetic Hallmark of Melanoma
- Author
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Lian, Christine Guo, Xu, Yufei, Ceol, Craig, Wu, Feizhen, Larson, Allison, Dresser, Karen, Xu, Wenqi, Tan, Li, Hu, Yeguang, Zhan, Qian, Lee, Chung-wei, Hu, Di, Lian, Bill Q., Kleffel, Sonja, Yang, Yijun, Neiswender, James, Khorasani, Abraham J., Fang, Rui, Lezcano, Cecilia, and Duncan, Lyn M.
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MELANOMA , *CYTOSINE derivatives , *EPIGENETICS , *DNA methylation , *HYDROXYLASES , *ISOCITRATE dehydrogenase , *GENETICS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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