The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
IDH mutation impairs histone demethylation and results in a block to cell differentiation
Open accessAbstract
Recurrent mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 have been identified in gliomas, acute myeloid leukaemias (AML) and chondrosarcomas, and share a novel enzymatic property of producing 2-hydroxyglutarate (2HG) from α-ketoglutarate. Here we report that 2HG-producing IDH mutants can prevent the histone demethylation that is required for lineage-specific progenitor cells to differentiate into terminally differentiated cells. In tumour samples from glioma patients, IDH mutations were associated with a distinct gene expression profile enriched for genes expressed in neural progenitor cells, and this was associated with increased histone methylation. To test whether the ability of IDH mutants to promote histone methylation contributes to a block in cell differentiation in non-transformed cells, we tested the effect of neomorphic IDH mutants on adipocyte differentiation in vitro. Introduction of either mutant IDH or cell-permeable 2HG was associated with repression of the inducible expression of lineage-specific differentiation genes and a block to differentiation. This correlated with a significant increase in repressive histone methylation marks without observable changes in promoter DNA methylation. Gliomas were found to have elevated levels of similar histone repressive marks. Stable transfection of a 2HG-producing mutant IDH into immortalized astrocytes resulted in progressive accumulation of histone methylation. Of the marks examined, increased H3K9 methylation reproducibly preceded a rise in DNA methylation as cells were passaged in culture. Furthermore, we found that the 2HG-inhibitable H3K9 demethylase KDM4C was induced during adipocyte differentiation, and that RNA-interference suppression of KDM4C was sufficient to block differentiation. Together these data demonstrate that 2HG can inhibit histone demethylation and that inhibition of histone demethylation can be sufficient to block the differentiation of non-transformed cells.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Mutant IDH protein produces a novel onco-metabolite, 2-hydroxyglutarate (2-HG), that interferes with iron-dependent hydroxylases, including the TET family of 5′-methylcytosine hydroxylases3–7.”
From Insulator dysfunction and oncogene activation in IDH mutant gliomas (2016) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For example, 2-HG acts as a competitive inhibitor of α-KG, and its production by mutant IDH1 consumes α-KG (81, 99), leading to reduced TET2 and JmjC activity in tumor cells (79, 80).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [80]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Therefore, it is plausible that increased levels of 2-HG may enable a switch to an entirely HIF-independent mechanism.”
From HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells (2021) · cites this paper as [154]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Mutant IDH protein produces a novel onco-metabolite, 2-hydroxyglutarate (2-HG), that interferes with iron-dependent hydroxylases, including the TET family of 5′-methylcytosine hydroxylases3–7.”
From Insulator dysfunction and oncogene activation in IDH mutant gliomas (2016) · cites this paper as [6]
In the citing paper
“In addition to its epigenetic effects, D-2HG inhibits enzymes from the canonical metabolic network (104). Such enzymes include transaminases that produce glutamate for glutathione biosynthesis, rendering IDH-mutant gliomas susceptible to treatments that deplete glutamate and enhance oxidative stress (105).”
From Metabolic reprogramming and cancer progression (2020) · cites this paper as [104]
In the citing paper
“The role of R-2-HG as an oncometabolite has been implicated in epigenetic modifications through the inhibition of α-KG-dependent dioxygenases and demethylases”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [118]
In the citing paper
“a neomorphic mutation in IDH1 and/or IDH2 causes a change in enzymatic activity and the accumulation of 2-hydroxyglutarate (2-HG), which inhibits the function of αKG-dependent enzymes such as TET2, resulting in the loss of 5hmC, an increase in DNA methylation and ultimately altered gene expression programmes that drive cancer development66.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [66]
In the citing paper
“By blocking the enzymatic activity of histone and DNA demethylases, d-2HG can function to lock cells in a hypermethylated state that blocks differentiation and reinforces a malignant and stem cell–like phenotype (30, 172, 173, 174).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [173]
In the citing paper
“In the cancer setting, 2-HG has been shown to influence a number of biological processes, including cell differentiation, DNA methylation, and histone methylation (79–82), leading to its classification as an oncometabolite.”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [80]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Verhaak, R. G. W., Hoadley, K. A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M. D., Miller, C. R., Ding, L., Golub, T., Mesirov, J. P., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.020 · Cited by 7,575
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
Parsons, D. W., Jones, S., Zhang, X., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.-M., Gallia, G. L., et al. (2008) · Science · doi:10.1126/science.1164382 · Cited by 5,857
IDH1 and IDH2 Mutations in Gliomas
Yan, H., Parsons, D. W., Jin, G., McLendon, R., Rasheed, B. A., Yuan, W., Kos, I., Batinic-Haberle, I., Jones, S., Riggins, G. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808710 · Cited by 5,847
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.041 · Cited by 5,361
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154
Self-citationXu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.-H., Ito, S., Yang, C., Wang, P., Xiao, M.-T., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.12.014 · Cited by 2,875
The complex language of chromatin regulation during transcription
Berger, S. L. (2007) · Nature · doi:10.1038/nature05915 · Cited by 2,768
Self-citationFigueroa, M. E., Abdel-Wahab, O., Lu, C., Ward, P. S., Patel, J., Shih, A., Li, Y., Bhagwat, N., Vasanthakumar, A., Fernandez, H. F., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.11.015 · Cited by 2,766
Self-citationIdentification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma
Noushmehr, H., Weisenberger, D. J., Diefes, K., Phillips, H. S., Pujara, K., Berman, B. P., Pan, F., Pelloski, C. E., Sulman, E. P., Bhat, K. P., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.03.017 · Cited by 2,337
ATP-citrate lyase links cellular metabolism to histone acetylation
Wellen, K. E., Hatzivassiliou, G., Sachdeva, U. M., Bui, T. V., Cross, J. R., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1164097 · Cited by 2,298
Self-citation
Cited by
Sorted by citations
Items 401–500 of 1,001
SIRT3-Mediated Dimerization of IDH2 Directs Cancer Cell Metabolism and Tumor Growth
Zou, X., Zhu, Y., Park, S., Liu, G., O’Brien, J., Jiang, H., & Gius, D. R. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2393 · Cited by 106
Stem cell signature in glioblastoma: therapeutic development for a moving target
Nakano, I. (2014) · Journal of neurosurgery · doi:10.3171/2014.9.jns132253 · Cited by 99
Glutamine Metabolism in Brain Tumors
Natarajan, S. K., & Venneti, S. (2019) · Cancers · doi:10.3390/cancers11111628 · Cited by 99
Spyropoulou, A., Gargalionis, A. N., Dalagiorgou, G., Adamopoulos, C., Papavassiliou, K. A., Lea, R. W., Piperi, C., & Papavassiliou, A. G. (2013) · NeuroMolecular Medicine · doi:10.1007/s12017-013-8254-x · Cited by 95
Glioblastoma Therapy Can Be Augmented by Targeting IDH1-Mediated NADPH Biosynthesis
Wahl, D. R., Dresser, J., Wilder-Romans, K., Parsels, J. D., Zhao, S. G., Davis, M. A., Zhao, L., Kachman, M. T., Wernisch, S., Burant, C., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-2008 · Cited by 97
Acute myeloid leukaemia genomics
Medinger, M., & Passweg, J. R. (2017) · British Journal of Haematology · doi:10.1111/bjh.14823 · Cited by 98
Nazeri, E., Gouran‐Savadkoohi, M., Majidzadeh‐A, K., & Esmaeili, R. (2018) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2018.09.001 · Cited by 95
The multifaceted contribution of α-ketoglutarate to tumor progression: An opportunity to exploit?
Abla, H., Sollazzo, M., Gasparre, G., Iommarini, L., & Porcelli, A. M. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.031 · Cited by 99
Mitochondrial DNA mutations in ageing and cancer
Smith, A. L. M., Whitehall, J. C., & Greaves, L. C. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13291 · Cited by 105
Molenaar, R. J., Thota, S., Nagata, Y., Patel, B. J., Clemente, M. J., Przychodzen, B. P., Hirsch, C. M., Viny, A. D., Hosano, N., Bleeker, F. E., et al. (2015) · Leukemia · doi:10.1038/leu.2015.91 · Cited by 101
Fan, B., Mellinghoff, I. K., Wen, P. Y., Lowery, M. A., Goyal, L., Tap, W. D., Pandya, S. S., Manyak, E. L., Jiang, L., Liu, G., et al. (2019) · Investigational New Drugs · doi:10.1007/s10637-019-00771-x · Cited by 94
Self-citationZhu, G. G., Nafa, K., Agaram, N. P., Zehir, A., Benayed, R., Sadowska, J., Borsu, L. A., Kelly, C. M., Tap, W. D., Fabbri, N., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-4212 · Cited by 94
Signaling pathways in brain tumors and therapeutic interventions
Li, S., Wang, C., Chen, J., Lan, Y., Zhang, W., Kang, Z., Zheng, Y., Zhang, R., Yu, J., & Li, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01260-z · Cited by 105
The TCA cycle as a bridge between oncometabolism and DNA transactions in cancer
Ciccarone, F., Vegliante, R., Leo, L. D., & Ciriolo, M. R. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.06.008 · Cited by 97
Wiestler, B., Claus, R., Hartlieb, S. A., Schliesser, M. G., Weiß, E. K., Hielscher, T., Platten, M., Dittmann, L. M., Meisner, C., Felsberg, J., et al. (2013) · Neuro-Oncology · doi:10.1093/neuonc/not043 · Cited by 93
Alghamri, M. S., McClellan, B. L., Avvari, R., Thalla, R., Carney, S. V., Hartlage, C. S., Haase, S., Ventosa, M., Taher, A. W., Kamran, N., et al. (2021) · Science Advances · doi:10.1126/sciadv.abh3243 · Cited by 89
Natsume, A., Arakawa, Y., Narita, Y., Sugiyama, K., Hata, N., Muragaki, Y., Shinojima, N., Kumabe, T., Saito, R., Motomura, K., et al. (2023) · Neuro-Oncology · doi:10.1093/neuonc/noac155 · Cited by 93
Polarizing Macrophages through Reprogramming of Glucose Metabolism
Blagih, J., & Jones, R. G. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.05.008 · Cited by 93
Deng, P., Chen, Q., Hong, C., & Wang, C. (2015) · International Journal of Oral Science · doi:10.1038/ijos.2015.41 · Cited by 93
TET2 in Normal and Malignant HematopoiesisPreprint
Bowman, R. L., & Levine, R. L. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026518 · Cited by 102
Self-citationFontebasso, A. M., Liu, X., Sturm, D., & Jabado, N. (2013) · Brain Pathology · doi:10.1111/bpa.12023 · Cited by 89
Molecular Subtypes of Glioblastoma Are Relevant to Lower Grade Glioma
Guan, X., Vengoechea, J. E., Zheng, S., Sloan, A. E., Chen, Y., Brat, D. J., O’Neill, B. P., de Groot, J., Yust‐Katz, S., Yung, W.-K. A., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091216 · Cited by 93
Epigenetic Enzyme Mutations: Role in Tumorigenesis and Molecular Inhibitors
Han, M., Jia, L., Lv, W., Wang, L., & Cui, W. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00194 · Cited by 99
The Role of D-3-Phosphoglycerate Dehydrogenase in Cancer
Zhao, X., Fu, J., Du, J., & Xu, W. (2020) · International Journal of Biological Sciences · doi:10.7150/ijbs.41051 · Cited by 93
Clinical significance of T cell metabolic reprogramming in cancer
Herbel, C., Patsoukis, N., Bardhan, K., Seth, P., Weaver, J. D., & Boussiotis, V. A. (2016) · Clinical and Translational Medicine · doi:10.1186/s40169-016-0110-9 · Cited by 99
SETting the Stage for Cancer Development: SETD2 and the Consequences of Lost MethylationPreprint
Fahey, C. C., & Davis, I. J. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026468 · Cited by 92
Epigenetics of myelodysplastic syndromes
Itzykson, R., & Fenaux, P. (2013) · Leukemia · doi:10.1038/leu.2013.343 · Cited by 91
Shelar, S. B., Shim, E., Brinkley, G. J., Kundu, A., Carobbio, F., Poston, T. L., Tan, J. C., Parekh, V., Benson, D. G., Crossman, D. K., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1727 · Cited by 89
Driver mutations in acute myeloid leukemia
Kishtagari, A., Levine, R. L., & Viny, A. D. (2020) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000567 · Cited by 100
Self-citationThe IDH-TAU-EGFR triad defines the neovascular landscape of diffuse gliomas
Gargini, R., Segura‐Collar, B., Herránz, B., García‐Escudero, V., Romero-Bravo, A., Núñez, F. J., García‐Pérez, D., Gutiérrez-Guamán, J., Ayuso‐Sacido, Á., Seoane, J., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aax1501 · Cited by 89
Wild-type isocitrate dehydrogenase under the spotlight in glioblastoma
Alzial, G., Renoult, O., Paris, F., Gratas, C., Clavreul, A., & Pecqueur, C. (2021) · Oncogene · doi:10.1038/s41388-021-02056-1 · Cited by 101
ADHFE1 is a breast cancer oncogene and induces metabolic reprogramming
Mishra, P., Tang, W., Putluri, V., Dorsey, T. H., Jin, F., Wang, F., Zhu, D., Amable, L., Deng, T., Zhang, S., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci93815 · Cited by 91
Precision therapy for lymphoma—current state and future directions
Intlekofer, A. M., & Younes, A. (2014) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2014.137 · Cited by 91
Nguyen, D. N., Heaphy, C. M., de Wilde, R. F., Orr, B. A., Odia, Y., Eberhart, C. G., Meeker, A. K., & Rodríguez, F. J. (2012) · Brain Pathology · doi:10.1111/j.1750-3639.2012.00630.x · Cited by 92
Danussi, C., Bose, P., Parthasarathy, P. T., Silberman, P. C., Arnam, J. S. V., Vitucci, M., Tang, O. Y., Heguy, A., Wang, Y., Chan, T. A.-T., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03476-6 · Cited by 91
Self-citationHyperpolarized [1-13C] Glutamate: A Metabolic Imaging Biomarker of IDH1 Mutational Status in Glioma
Chaumeil, M. M., Larson, P. E. Z., Woods, S. M., Cai, L., Eriksson, P., Robinson, A. E., Lupo, J., Vigneron, D. B., Nelson, S. J., Pieper, R. O., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0680 · Cited by 87
Rare insights into cancer biology
Adam, J., Yang, M., Soga, T., & Pollard, P. J. (2013) · Oncogene · doi:10.1038/onc.2013.222 · Cited by 90
Molecular Pathways: Metabolic Control of Histone Methylation and Gene Expression in Cancer
Tran, T. Q., Lowman, X. H., & Kong, M. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2506 · Cited by 91
Zhang, L., Sørensen, M. D., Kristensen, B. W., Reifenberger, G., McIntyre, T. M., & Lin, F. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3855 · Cited by 93
Advances in Research of Adult Gliomas
Finch, A., Solomou, G., Wykes, V., Pohl, U., Bardella, C., & Watts, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020924 · Cited by 91
D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in micePreprint
Akbay, E. A., Moslehi, J. J., Christensen, C. L., Saha, S. K., Tchaicha, J. H., Ramkissoon, S. H., Stewart, K. M., Carretero, J., Kikuchi, E., Zhang, H., et al. (2014) · Genes & Development · doi:10.1101/gad.231233.113 · Cited by 93
Self-citationContext-dependent actions of Polycomb repressors in cancer
Koppens, M. A. J., & van Lohuizen, M. (2015) · Oncogene · doi:10.1038/onc.2015.195 · Cited by 88
Qu, Y., Lennartsson, A., Gaidzik, V. I., Deneberg, S., Karimi, M., Bengtzén, S., Höglund, M., Bullinger, L., Döhner, K., & Lehmann, S. (2014) · Epigenetics · doi:10.4161/epi.29315 · Cited by 92
Hollinshead, K. E. R., Munford, H., Eales, K. L., Bardella, C., Li, C., Escribano-Gonzalez, C., Thakker, A., Nonnenmacher, Y., Kľučková, K., Jeeves, M., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.084 · Cited by 92
Genetically-defined metabolic reprogramming in cancer
Mullen, A. R., & DeBerardinis, R. J. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.06.009 · Cited by 90
D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2
Lin, A., Abbas, S., Kim, S., Ortega, M. M., Bouamar, H., Escobedo, Y. A., Varadarajan, P., Qin, Y., Sudderth, J., Schulz, E., et al. (2015) · Nature Communications · doi:10.1038/ncomms8768 · Cited by 88
The evolving genomic landscape of myeloproliferative neoplasms
Nangalia, J., & Green, T. R. (2014) · Hematology · doi:10.1182/asheducation-2014.1.287 · Cited by 87
Boutzen, H., Saland, E., Larrue, C., de Toni, F., Gales, L., Castelli, F. A., Cathebas, M., Zaghdoudi, S., Stuani, L., Kaoma, T., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20150736 · Cited by 92
Updates in prognostic markers for gliomas
Aquilanti, E., Miller, J. J., Santagata, S., Cahill, D. P., & Brastianos, P. K. (2018) · Neuro-Oncology · doi:10.1093/neuonc/noy158 · Cited by 88
Epigenetic therapy combinations in acute myeloid leukemia: what are the options?
Bewersdorf, J. P., Shallis, R. M., Stahl, M. F., & Zeidan, A. M. (2019) · Therapeutic Advances in Hematology · doi:10.1177/2040620718816698 · Cited by 88
Cellular Senescence: Mechanisms and Therapeutic Potential
Liao, Z., Yeo, H. L., Wong, S. W., & Zhao, Y. X. (2021) · Biomedicines · doi:10.3390/biomedicines9121769 · Cited by 89
Jiang, L., Boufersaoui, A., Yang, C., Ko, B., Rakheja, D., Guevara, G., Hu, Z., & DeBerardinis, R. J. (2016) · Metabolic Engineering · doi:10.1016/j.ymben.2016.11.004 · Cited by 84
Friend or foe—IDH1 mutations in glioma 10 years on
Huang, L. E. (2019) · Carcinogenesis · doi:10.1093/carcin/bgz134 · Cited by 84
Metabolite sensing and signaling in cancer
Wang, Y.-P., Li, J., Qu, J., Yin, M., & Lei, Q. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev119.007624 · Cited by 87
Mukherjee, J., Johannessen, T.-C. A., Ohba, S., Chow, T. T., Jones, L. E., Pandita, A., & Pieper, R. O. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-2269 · Cited by 87
Choi, C., Ganji, S., Hulsey, K., Madan, A., Kovács, Z. Z., Dimitrov, I. E., Zhang, S., Pichumani, K., Mendelsohn, D. B., Mickey, B., et al. (2013) · NMR in Biomedicine · doi:10.1002/nbm.2943 · Cited by 83
Badur, M. G., Muthusamy, T., Parker, S. J., Ma, S., McBrayer, S. K., Cordes, T., Magaña, J. H., Guan, K., & Metallo, C. M. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.09.074 · Cited by 87
Unruh, D. J., Zewde, M. G., Buss, A., Drumm, M. R., Tran, A. N., Scholtens, D. M., & Horbinski, C. (2019) · Scientific Reports · doi:10.1038/s41598-019-45346-1 · Cited by 91
IDH Mutations in Glioma: Double-Edged Sword in Clinical Applications?
Kayabölen, A., Yilmaz, E., & Onder, T. B. (2021) · Biomedicines · doi:10.3390/biomedicines9070799 · Cited by 88
Epigenetics in the hematologic malignancies
Fong, C. Y., Morison, J., & Dawson, M. A. (2014) · Haematologica · doi:10.3324/haematol.2013.092007 · Cited by 87
Morel, D., Almouzni, G., Soria, J., & Postel-Vinay, S. C. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw552 · Cited by 87
Molecular Pathways in Gliomagenesis and Their Relevance to Neuropathologic Diagnosis
Appin, C., & Brat, D. J. (2014) · Advances in Anatomic Pathology · doi:10.1097/pap.0000000000000048 · Cited by 86
Metabolic tricks of cancer cells
Hönigová, K., Navrátil, J., Peltanová, B., Polanska, H. H., Raudenská, M., & Masařík, M. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2022.188705 · Cited by 84
Interactions between epigenetics and metabolism in cancers
Yun, J., Johnson, J. L., Hanigan, C. L., & Locasale, J. W. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00163 · Cited by 82
D-2-Hydroxyglutarate in Glioma Biology
Chou, F.-J., Liu, Y., Lang, F., & Yang, C. (2021) · Cells · doi:10.3390/cells10092345 · Cited by 87
Ohba, S., Mukherjee, J., See, W. L., & Pieper, R. O. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0924 · Cited by 84
Metabolic Reprogramming in Mutant IDH1 Glioma Cells
Izquierdo-García, J. L., Viswanath, P., Eriksson, P., Chaumeil, M. M., Pieper, R. O., Phillips, J. J., & Ronen, S. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0118781 · Cited by 90
Classe, M., Yao, H., Mouawad, R., Creighton, C. J., Burgess, A., Allanic, F., Wassef, M., Leroy, X., Vérillaud, B., Mortuaire, G., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.09.047 · Cited by 81
de la Fuente, M. I., Colman, H., Rosenthal, M. A., Tine, B. A. V., Levacic, D., Walbert, T., Gan, H. K., Vieito, M., Milhem, M. M., Lipford, K., et al. (2022) · Neuro-Oncology · doi:10.1093/neuonc/noac139 · Cited by 82
Jeffery, C. J. (2015) · Journal of Proteomics · doi:10.1016/j.jprot.2015.10.003 · Cited by 83
Update on Targets and Novel Treatment Options for High-Grade Osteosarcoma and Chondrosarcoma
van Oosterwijk, J. G., Anninga, J., Gelderblom, H. A. J., Cleton-Jansen, A., & Bovée, J. V. M. G. (2013) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2013.07.012 · Cited by 81
Mutant IDH1 Enhances the Production of 2-Hydroxyglutarate Due to Its Kinetic Mechanism
Rendina, A. R., Pietrak, B., Smallwood, A. M., Zhao, H., Qi, H., Quinn, C. J., Adams, N. D., Concha, N. O., Duraiswami, C., Thrall, S. H., et al. (2013) · Biochemistry · doi:10.1021/bi400514k · Cited by 81
The oncogenic potential of Jumonji D2 (JMJD2/KDM4) histone demethylase overexpression
Young, L. C., & Hendzel, M. J. (2012) · Biochemistry and Cell Biology · doi:10.1139/bcb-2012-0054 · Cited by 80
Thompson, A. A. R., Dickinson, R. S., Murphy, F. A., Thomson, J. P., Marriott, H. M., Tavares, A., Willson, J. A., Williams, L., Lewis, A., Mirchandani, A. S., et al. (2017) · Science Immunology · doi:10.1126/sciimmunol.aal2861 · Cited by 78
Non-enzymatic chemistry enables 2-hydroxyglutarate-mediated activation of 2-oxoglutarate oxygenases
Tarhonskaya, H., Rydzik, A. M., Leung, I. K. H., Loik, N. D., Chan, M. C., Kawamura, A., McCullagh, J. S. O., Claridge, T. D. W., Flashman, E., & Schofield, C. J. (2014) · Nature Communications · doi:10.1038/ncomms4423 · Cited by 80
Cell Surface Notch Ligand DLL3 is a Therapeutic Target in Isocitrate Dehydrogenase–mutant Glioma
Spino, M., Kurz, S. C., Chiriboga, L. A., Serrano, J., Zeck, B., Sen, N., Patel, S. V., Shen, G., Vasudevaraja, V., Tsirigos, A., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2312 · Cited by 80
Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells
Reitman, Z. J., Paolella, B. R., Bergthold, G., Pelton, K., Becker, S., Jones, R. E., Sinai, C. E., Malkin, H., Huang, Y., Grimmett, L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11493-2 · Cited by 78
Price, G. A., Bouras, A., Hambardzumyan, D., & Hadjipanayis, C. G. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103453 · Cited by 79
Biomarker-driven diagnosis of diffuse gliomas
Appin, C., & Brat, D. J. (2015) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2015.05.002 · Cited by 84
Li, H., Chawla, G., Hurlburt, A. J., Sterrett, M. C., Zaslaver, O., Cox, J. E., Karty, J. A., Rosebrock, A. P., Caudy, A. A., & Tennessen, J. M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1614102114 · Cited by 76
Elhammali, A., Ippolito, J. E., Collins, L., Crowley, J., Marasa, J., & Piwnica-Worms, D. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0572 · Cited by 77
2-HG Inhibits Necroptosis by Stimulating DNMT1-Dependent Hypermethylation of the RIP3 Promoter
Yang, Z., Jiang, B., Wang, Y., Ni, H., Zhang, J., Xia, J., Shi, M., Hung, L.-M., Ruan, J., Mak, T. W., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.012 · Cited by 78
Chromatin modifiers and the promise of epigenetic therapy in acute leukemia
Greenblatt, S. M., & Nimer, S. D. (2014) · Leukemia · doi:10.1038/leu.2014.94 · Cited by 83
Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases by 2-Thiohydantoin Compounds
Wu, F., Jiang, H., Zheng, B., Kogiso, M., Yao, Y., Zhou, C., Li, X., & Song, Y. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00684 · Cited by 78
High-Dose Vitamin C for Cancer Therapy
Mussa, A., Idris, R. A. M., Ahmed, N., Ahmad, S., Murtadha, A. H., Din, T. A. D. A. T., Yean, C. Y., Rahman, W. F. W. A., Lazim, N. M., Uskoković, V., et al. (2022) · Pharmaceuticals · doi:10.3390/ph15060711 · Cited by 85
Mutations in the Isocitrate Dehydrogenase Genes IDH1 and IDH2 in Tumors
Schaap, F. G., French, P. J., & Bovée, J. V. M. G. (2012) · Advances in Anatomic Pathology · doi:10.1097/pap.0b013e31827b654d · Cited by 80
Molecular Genetic Markers in Acute Myeloid Leukemia
Yohe, S. L. (2015) · Journal of Clinical Medicine · doi:10.3390/jcm4030460 · Cited by 82
Metabolic regulation of stem cell function
Burgess, R., Agathocleous, M., & Morrison, S. J. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12247 · Cited by 81
Reconstructing the molecular life history of gliomas
Barthel, F. P., Wesseling, P., & Verhaak, R. G. W. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1842-y · Cited by 86
Normal Hematopoiesis Is a Balancing Act of Self-Renewal and RegenerationPreprint
Olson, O. C., Kang, Y.-A., & Passegue, E. A. (2020) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a035519 · Cited by 89
Boehme, K. A., Schleicher, S., Traub, F., & Rolauffs, B. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010311 · Cited by 77
Targeting Metabolism to Induce Cell Death in Cancer Cells and Cancer Stem Cells
Pecqueur, C., Oliver, L., Oizel, K., Lalier-Bretaudeau, L., & Vallette, F. M. (2013) · International Journal of Cell Biology · doi:10.1155/2013/805975 · Cited by 83
Pedersen, M. T., Agger, K., Laugesen, A., Johansen, J. V., Cloos, P. A., Christensen, J. F., & Helin, K. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00864-13 · Cited by 75
Chromatin-modifying agents in anti-cancer therapy
Seidel, C., Florean, C., Schnekenburger, M., Dicato, M. A., & Diederich, M. F. (2012) · Biochimie · doi:10.1016/j.biochi.2012.05.012 · Cited by 79
Metabolic determinants of tumour initiation
Brunner, J. S., & Finley, L. W. S. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00773-5 · Cited by 78
Nagashima, H., Tanaka, K., Sasayama, T., Irino, Y., Sato, N., Takeuchi, Y., Kyotani, K., Mukasa, A., Mizukawa, K., Sakata, J., et al. (2016) · Neuro-Oncology · doi:10.1093/neuonc/now090 · Cited by 76
A Review of Radiomics and Deep Predictive Modeling in Glioma Characterization
Gore, S. A., Chougule, T., Jagtap, J., Saini, J. S., & Ingalhalikar, M. (2020) · Academic Radiology · doi:10.1016/j.acra.2020.06.016 · Cited by 80
Crystallographic Investigation and Selective Inhibition of Mutant Isocitrate Dehydrogenase
Zheng, B., Yao, Y., Liu, Z., Deng, L., Anglin, J. L., Jiang, H., Prasad, B. V. V., & Song, Y. (2013) · ACS Medicinal Chemistry Letters · doi:10.1021/ml400036z · Cited by 76
Fathi, A. T., Sadrzadeh, H., Comander, A. H., Higgins, M. J., Bardia, A., Perry, A. M., Burke, M. E., Silver, R. M., Matulis, C. R., Straley, K. S., et al. (2014) · The Oncologist · doi:10.1634/theoncologist.2013-0417 · Cited by 77
Becker‐Kettern, J., Paczia, N., Conrotte, J., Kay, D. P., Guignard, C., Jung, P. P., & Linster, C. L. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.704494 · Cited by 76
Metadata
- Authors
- Lu, C., Ward, P. S., Kapoor, G. S., Rohle, D., Turcan, S., Abdel-Wahab, O., Edwards, C. R., Khanin, R., Figueroa, M. E., Melnick, A., Wellen, K. E., O’Rourke, D. M., Berger, S. L., Chan, T. A., Levine, R. L., Mellinghoff, I. K., & Thompson, C. B.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- University of Pennsylvania (US)
- Weill Cornell Medicine (US)
- Corresponding author
- Thompson, Craig B.
- ORCID
- Venue
- Nature
- Published
- 2012-02-15
- Volume
- 483
- Issue
- 7390
- Pages
- 474-478
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3478770
- OpenAlex
- W2154313451
- Cited by
- 1,985
- References
- 30
- Citations by year
- 2026: 81 · 2025: 93 · 2024: 106 · 2023: 125 · 2022: 122 · 2021: 180 · 2020: 170 · 2019: 153 · 2018: 146 · 2017: 163 · 2016: 151 · 2015: 123 · 2014: 138 · 2013: 136 · 2012: 91
- FWCI
- 74.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- University of Pennsylvania
- National Cancer Institute (R01CA078831, R01CA105463, U54CA143798)
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- 2-hydroxyglutarate, histone demethylation, histone methylation, glioma, oncometabolites, DNA hypermethylation, hypoxia-inducible factor, adipogenesis, neural progenitor cells
- MeSH terms
- Animals, Astrocytes, Cell Differentiation, Enzyme Induction, Gene Expression Regulation, Glioma, Glutarates, Histones, Humans, Isocitrate Dehydrogenase, Methylation, Mutation, Promoter Regions, Genetic, Adipocytes, Cell Lineage, DNA Methylation, 3T3-L1 Cells, Cell Line, Tumor, Mice, Jumonji Domain-Containing Histone Demethylases, HEK293 Cells, Neural Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
