LOSS OF 5-HYDROXYMETHYLCYTOSINE IS AN EPIGENETIC HALLMARK OF MELANOMA

By C. Lian, Yufei Xu, C. Ceol, Feizhen Wu, A. Larson, K. Dresser, Wenjie Xu, Li Tan, Yeguang Hu, Q. Zhan and 21 more. Cell, 2012

771 citations recorded by the source corpus.

SUMMARY DNA methylation at the 5-position of cytosine (5-mC) is a key epigenetic mark 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 5-hmC landscape in the melanoma epigenome. We show that down-regulation 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/21652a5c63e394f32c501e6c56ec5c97b21fd86f

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In Cancer Research

1. Hao Wu

In Molecular Biology

1. Hao Wu
2. Yi Zhang
3. K. Helin
4. Yingming Zhao
5. A. Carr
6. Peter A. Jones
7. J. Simon
8. D. Reinberg

Citations in the corpus

• SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways (2013, background): “, 2010), whereas its downregulation leads to epigenetic dysfunction via the loss of 5-hydroxymethyl-cytosine in melanoma (Lian et al., 2012).”
• The Roles of Vitamin C in Skin Health (2017, background): “Aberrant epigenetic alterations are thought to have a role in cancer progression, and there is data to suggest that a loss of 5 hmC occurs during the early development and progression of melanoma [114].”
• Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions (2014, positive): “Recent studies suggest that transcriptional downregulation of all three TET genes and IDH1/2 is observed in many solid cancers that are not known to be associated with mutations in these enzymes, and global loss of 5hmC may be broadly used as a diagnostic biomarker for human melanoma, breast, liver,”
• Role of TET enzymes in DNA methylation, development, and cancer (2016, background): “Nonetheless, decreased expression of TET proteins and lower 5hmC levels are general hallmarks of many cancer types, including gastric, prostate, liver, lung, and breast cancer as well as glioblastoma and melanoma (Kudo et al. 2012; Lian et al. 2012; Turcan et al. 2012; Liu et al. 2013a; Yang et al. ”