The DOI matches its Crossref record; 39 of the 40 references it cites were found in a registry or an index.
Loss of 5-Hydroxymethylcytosine Is an Epigenetic Hallmark of Melanoma
Open accessAbstract
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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“whereas its downregulation leads to epigenetic dysfunction via the loss of 5-hydroxymethyl-cytosine in melanoma (Lian et al., 2012).”
From SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways (2013) · cites this paper as Lian et al., 2012
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Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., et al. (2009) · Science · doi:10.1126/science.1170116 · Cited by 5,836
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Self-citationIto, S., D’Alessio, A. C., Taranova, O., Hong, K., Sowers, L. C., & Zhang, Y. (2010) · Nature · doi:10.1038/nature09303 · Cited by 2,628
Ward, P. S., Patel, J., Wise, D. R., Abdel-Wahab, O., Bennett, B. D., Coller, H. A., Cross, J. R., Fantin, V. R., Hedvat, C. V., Perl, A. E., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.01.020 · Cited by 2,020 · cited 2×
“These data suggest that IDH2, but not IDH1, is specifically downregulated in melanomas and that the WT IDH2 acts as a putative tumor suppressor in the zebrafish melanoma model, although the IDH family of enzymes has been considered candidate oncogenes in various tumors (Ward et al., 2010; Wrzeszczynski et al., 2011).”
BackgroundMutation in TET2 in Myeloid Cancers
Delhommeau, F., Dupont, S., Valle, V. D., James, C., Trannoy, S., Massé, A., Kosmider, O., Le Couedic, J.-P., Robert, F., Alberdi, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810069 · Cited by 1,776
Identification of cells initiating human melanomas
Schatton, T., Murphy, G. F., Frank, N. Y., Yamaura, K., Waaga-Gasser, A. M., Gasser, M., Zhan, Q., Jordan, S., Duncan, L. M., Weishaupt, C., et al. (2008) · Nature · doi:10.1038/nature06489 · Cited by 1,449
Self-citationDynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation
Ficz, G., Branco, M. R., Seisenberger, S., Santos, F., Krueger, F., Hore, T. A., Marques, C. J., Andrews, S., & Reik, W. (2011) · Nature · doi:10.1038/nature10008 · Cited by 1,160
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TET-mediated active DNA demethylation: mechanism, function and beyond
Wu, X., & Zhang, Y. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.33 · Cited by 1,661
Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials
Cheng, Y., He, C., Wang, M., Ma, X., Mo, F., Yang, S., Han, J., & Wei, X. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0095-0 · Cited by 1,097
Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions
Wu, H., & Zhang, Y. (2014) · Cell · doi:10.1016/j.cell.2013.12.019 · Cited by 1,065
Role of TET enzymes in DNA methylation, development, and cancer
Rasmussen, K. D., & Helin, K. (2016) · Genes & Development · doi:10.1101/gad.276568.115 · Cited by 1,040
“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. 2013).”
BackgroundSIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways
Park, J., Chen, Y., Tishkoff, D. X., Peng, C., Tan, M., Dai, L., Xie, Z., Zhang, Y., Zwaans, B. M. M., Skinner, M. E., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.06.001 · Cited by 1,000
Metadata
- Authors
- Lian, C. G., Xu, Y., Ceol, C., Wu, F., Larson, A., Dresser, K., Xu, W., Tan, L., Hu, Y., Zhan, Q., Lee, C.-W., Hu, D., Lian, B. Q., Kleffel, S., Yang, Y., Neiswender, J., Khorasani, A. J., Fang, R., Lezcano, C., Duncan, L. M., Scolyer, R. A., Thompson, J. F., Kakavand, H., Houvras, Y., Zon, L. I., Mihm, M. C., Kaiser, U. B., Schatton, T., Woda, B. A., Murphy, G. F., & Shi, Y. G.
- Affiliations
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Fudan University (CN)
- University of Massachusetts Chan Medical School (US)
- Ziopharm Oncology (United States) (US)
- Harvard University (US)
- The University of Sydney (AU)
- Corresponding author
- Shi, Yujiang G.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 150
- Issue
- 6
- Pages
- 1135-1146
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3770275
- OpenAlex
- W2029746613
- Cited by
- 789
- References
- 40
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 34 · 2023: 32 · 2022: 53 · 2021: 56 · 2020: 53 · 2019: 60 · 2018: 67 · 2017: 75 · 2016: 76 · 2015: 73 · 2014: 86 · 2013: 71 · 2012: 8
- FWCI
- 30.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 380 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Ministry of Education of the People's Republic of China
- Fudan University
- National Institutes of Health (5P50CA093683-09)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- 5-hydroxymethylcytosine, melanoma, DNA methylation, TET enzymes, IDH2, TET2, epigenetic cancer therapy, tumor suppressor, prognostic factors, melanoma progression
- MeSH terms
- Cytosine, DNA-Binding Proteins, Humans, Isocitrate Dehydrogenase, Melanocytes, Melanoma, Nevus, Proto-Oncogene Proteins, Gene Expression Regulation, Neoplastic, Epigenesis, Genetic, 5-Methylcytosine, Dioxygenases, Genome-Wide Association Study
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