Efficient induction of differentiation and growth inhibition in IDH1 mutant glioma cells by the DNMT inhibitor decitabine
Open accessAbstract
// Sevin Turcan 1,* , Armida W. M. Fabius 1,* , Alexandra Borodovsky 2 , Alicia Pedraza 1 , Cameron Brennan 1 , Jason Huse 1 , Agnes Viale 3 , Gregory J. Riggins 2 , and Timothy A. Chan 1,4,5 1 Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. 2 Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD. 3 Genomics Core, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 4 Dept. of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 5 Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. * These authors contributed equally to this work Correspondence: Timothy A. Chan, email: // Keywords : glioma, isocitrate dehydrogenase, methylation, epigenetics, treatment Received : September 12, 2013 Accepted : September 16, 2013 Published : September 16, 2013 Abstract Mutation in the IDH1 or IDH2 genes occurs frequently in gliomas and other human malignancies. In intermediate grade gliomas, IDH1 mutation is found in over 70% of tumors. These mutations impart the mutant IDH enzyme with a neomorphic activity – the ability to synthesize 2-hydroxyglutarate (2-HG). This ability leads to a reprogramming of chromatin state, a block in differentiation, and the establishment of the glioma hypermethylator phenotype (G-CIMP). It has been hypothesized but not proven that the extensive DNA methylation that occurs in G-CIMP tumors helps maintain and “lock in” glioma cancer cells in a dedifferentiated state. Here, we tested this hypothesis by treating patient derived IDH1 mutant glioma initiating cells (GIC) with non-cytotoxic, epigenetically targeted doses of the DNMT inhibitor decitabine. Global methylome analysis of treated IDH1 mutant GICs showed that DAC treatment resulted in reversal of DNA methylation marks induced by IDH and the re-expression of genes associated with differentiation. Accordingly, treatment of IDH1 mutant glioma cells resulted in a dramatic loss of stem-like properties and efficient adoption of markers of differentiation, effects not seen in decitabine treated IDH wild-type GICs. Induction of differentiation was much more efficient than that seen following treatment with a specific inhibitor of mutant IDH enzyme (Agios). Decitabine also decreased replicative potential and tumor growth in vivo . Reexpression of polycomb regulated genes accompanied these DAC-induced phenotypes. In total, our data indicates that targeting the pathologic DNA methylation in IDH mutant cells can reverse mutant IDH induced hypermethylation and block in differentiation and promote tumor control. These findings have substantial impact for exploring new treatment strategies for patients with IDH mutant gliomas.
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
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?
Mutant IDH inhibitors may not be effective in all IDH-mutant cancers; in many IDH-mutant glioma models they fail to reverse epigenetic changes or inhibit tumor proliferation despite lowering 2-HG.
“Despite success in some preclinical models and patients with AML, mutant IDH inhibitors may not be effective in all IDH-mutant cancers. For example, these drugs are unable to reverse epigenetic changes or inhibit tumor proliferation in many models of IDH mutant glioma, despite a robust ability to lower 2-HG in cells and tumors (Tateishi et al., 2015; Turcan et al., 2013).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Turcan et al., 2013
Tumors harboring an IDH mutation have increased sensitivity to hypomethylating agents, electron transport chain inhibitors, depletion of NAD+, and chemoradiotherapy.
“For example, tumors harboring an IDH mutation have increased sensitivity to hypomethylating agents (Turcan et al., 2013), electron transport chain inhibitors (Grassian et al., 2014), depletion of the coenzyme NAD+ (Tateishi et al., 2015) and chemoradiotherapy (Cairncross et al., 2014).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Turcan et al., 2013
Sensitivity to mutant IDH inhibitors appears to differ between leukemia and solid tumor models.
“Even among cancers where mutant IDH is an oncogenic driver, sensitivity to mutant IDH inhibitors appears to differ between leukemia and solid tumor models (Tateishi et al., 2015; Turcan et al., 2013).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Turcan et al., 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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 · see citing works
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 · see citing works
Self-citation<i>IDH1</i> and <i>IDH2</i> 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 · see citing works
Self-citationCancer-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 · see citing works
Xu, 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 · see citing works
Figueroa, 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 · see citing works
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 · see citing works
IDH mutation impairs histone demethylation and results in a block to cell differentiation
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., et al. (2012) · Nature · doi:10.1038/nature10860 · Cited by 1,985 · see citing works
Self-citationIDH1 mutation is sufficient to establish the glioma hypermethylator phenotype
Turcan, S., Rohle, D., Goenka, A., Walsh, L. A., Fang, F., Yilmaz, E., Campos, C., Fabius, A. W. M., Lu, C., Ward, P. S., et al. (2012) · Nature · doi:10.1038/nature10866 · Cited by 1,974 · see citing works
Self-citationCellular differentiation, cytidine analogs and DNA methylation
Jones, P. A., & Taylor, S. M. (1980) · Cell · doi:10.1016/0092-8674(80)90237-8 · Cited by 1,831 · see citing works
An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells
Rohle, D., Popovici-Muller, J., Palaskas, N., Turcan, S., Grommes, C., Campos, C., Tsoi, J., Clark, O., Oldrini, B., Komisopoulou, E., et al. (2013) · Science · doi:10.1126/science.1236062 · Cited by 1,153 · see citing works
Self-citationJuergens, R. A., Wrangle, J. M., Vendetti, F. P., Murphy, S. C., Zhao, M., Coleman, B., Sebree, R., Rodgers, K., Hooker, C. M., Franco, N. C., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0214 · Cited by 686 · see citing works
Tsai, H.-C., Li, H., Neste, L. V., Cai, Y., Robert, C., Rassool, F. V., Shin, J., Harbom, K., Beaty, R. M., Pappou, E. P., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2011.12.029 · Cited by 651 · see citing works
Epigenetic Resensitization to Platinum in Ovarian Cancer
Matei, D., Fang, F., Shen, C., Schilder, J., Arnold, A., Zeng, Y., Berry, W. A., Huang, T., & Nephew, K. P. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-3909 · Cited by 390 · see citing works
A heterozygous IDH1R132H/WT mutation induces genome-wide alterations in DNA methylationPreprint
Duncan, C. G., Barwick, B. G., Jin, G., Rago, C., Kapoor-Vazirani, P., Powell, D. R., Chi, J., Bigner, D. D., Vertino, P. M., & Yan, H. (2012) · Genome Research · doi:10.1101/gr.132738.111 · Cited by 176 · see citing works
Pinto, A., Attadia, V., Fusco, A., Ferrara, F., Spada, O., & Fiore, P. D. (1984) · Blood · doi:10.1182/blood.v64.4.922.922 · Cited by 175 · see citing works
Borodovsky, A., Salmasi, V., Turcan, Ş., Fabius, A. W. M., Baía, G. S., Eberhart, C. G., WEINGART, J. D., Gallia, G. L., Baylin, S. B., Chan, T. A.-T., et al. (2013) · Oncotarget · doi:10.18632/oncotarget.1408 · Cited by 156 · see citing works
Self-citationThe transcriptional repressor NIPP1 is an essential player in EZH2-mediated gene silencing
Nuytten, M., Beke, L., Eynde, A. V., Ceulemans, H., Beullens, M., Hummelen, P. V., Fuks, F., & Bollen, M. (2007) · Oncogene · doi:10.1038/sj.onc.1210774 · Cited by 78 · see citing works
Plasma and cerebrospinal fluid pharmacokinetics of 5-Aza-2'-deoxycytidine in rabbits and dogs.
Chabot, G. G., Rivard, G. E., & Momparler, R. L. (1983) · PubMed · Cited by 77 · see citing works
Mass Spectrometrical Analysis of Galectin Proteins in Primary Rat Cerebellar Astrocytes
Yang, J.-W., Kang, S. U., Engidawork, E., Rodrigo, R., Felipo, V., & Lubec, G. (2006) · Neurochemical Research · doi:10.1007/s11064-006-9100-4 · Cited by 10 · see citing works
Flagged first, then by citations
1 of the 21 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Epigenetic Determinants of CancerPreprint
Baylin, S. B., & Jones, P. A. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a019505 · Cited by 1,363 · see citing works
Targeting the cancer epigenome for therapy
Jones, P. A., Issa, J. J., & Baylin, S. B. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.93 · Cited by 1,132 · see citing works
Weller, M., Wick, W., Aldape, K. D., Brada, M., Berger, M. S., Pfister, S. M., Nishikawa, R., Rosenthal, M. A., Wen, P. Y., Stupp, R., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.17 · Cited by 1,130 · see citing works
Targeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971 · see citing works
Cancer Epigenetics: Tumor Heterogeneity, Plasticity of Stem-like States, and Drug Resistance
Easwaran, H., Tsai, H.-C., & Baylin, S. B. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.015 · Cited by 915 · see citing works
IDH mutation in glioma: molecular mechanisms and potential therapeutic targets
Han, S., Liu, Y., Cai, S. J., Qian, M., Ding, J., Larion, M., Gilbert, M. R., & Yang, C. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0814-x · Cited by 661 · see citing works
Metabolomics in cancer research and emerging applications in clinical oncology
Schmidt, D. R., Patel, R., Kirsch, D. G., Lewis, C. A., Heiden, M. G. V., & Locasale, J. W. (2021) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21670 · Cited by 652 · see citing works
Weller, M., Wen, P. Y., Chang, S. M., Dirven, L., Lim, M. K., Monje, M., & Reifenberger, G. (2024) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00516-y · Cited by 645 · see citing works
Glioma epigenetics: From subclassification to novel treatment options
Gusyatiner, O., & Hegi, M. E. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.11.010 · Cited by 547 · see citing works
IDH mutations in cancer and progress toward development of targeted therapeutics
Dang, L., Yen, K., & Attar, E. C. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw013 · Cited by 509 · see citing works
Differentiation therapy revisited
de Thé, H. (2018) · Nature reviews. Cancer · doi:10.1038/nrc.2017.103 · Cited by 462 · see citing works
Yuan, S., Norgard, R. J., & Stanger, B. Z. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0015 · Cited by 458 · see citing works
Extreme vulnerability of IDH1 mutant cancers to NAD+ depletion
Tateishi, K., Wakimoto, H., Iafrate, A. J., Tanaka, S., Loebel, F., Lelic, N., Wiederschain, D., Bedel, O., Deng, G., Zhang, B., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.11.006 · Cited by 433 · see citing works
Metabolic control of epigenetics in cancer
Kinnaird, A. S., Zhao, S., Wellen, K. E., & Michelakis, E. D. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.82 · Cited by 419 · see citing works
The implications of IDH mutations for cancer development and therapy
Pirozzi, C. J., & Yan, H. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00521-0 · Cited by 402 · see citing works
Miroshnikova, Y. A., Mouw, J. K., Barnes, J. M., Pickup, M. W., Lakins, J. N., Kim, Y., Lobo, K. A., Persson, A. I., Reis, G. F., McKnight, T. R., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3429 · Cited by 380 · see citing works
Biological Role and Therapeutic Potential of IDH Mutations in Cancer
Waitkus, M. S., Diplas, B. H., & Yan, H. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.04.011 · Cited by 334 · see citing works
Metabolic Codependencies in the Tumor Microenvironment
Dey, P., Kimmelman, A. C., & DePinho, R. A. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1211 · Cited by 342 · see citing works
Glioma CpG island methylator phenotype (G-CIMP): biological and clinical implications
Malta, T. M., de Souza, C. F., Sabedot, T. S., Silva, T. C., Mosella, M. S., Kalkanis, S. N., Snyder, J., Castro, A. V. B., & Noushmehr, H. (2017) · Neuro-Oncology · doi:10.1093/neuonc/nox183 · Cited by 302 · see citing works
Isocitrate dehydrogenase mutations in gliomas
Waitkus, M. S., Diplas, B. H., & Yan, H. (2015) · Neuro-Oncology · doi:10.1093/neuonc/nov136 · Cited by 282 · see citing works
Im, A., Sehgal, A. R., Carroll, M. P., Smith, B. D., Tefferi, A., Johnson, D. E., & Boyiadzis, M. M. (2014) · Leukemia · doi:10.1038/leu.2014.124 · Cited by 266 · see citing works
Interplay between epigenetics and metabolism in oncogenesis: mechanisms and therapeutic approaches
Wong, C. C., Qian, Y., & Yu, J. Q. (2017) · Oncogene · doi:10.1038/onc.2016.485 · Cited by 260 · see citing works
Mutant Isocitrate Dehydrogenase Inhibitors as Targeted Cancer Therapeutics
Golub, D., Iyengar, N. S., Dogra, S., Wong, T., Bready, D., Tang, K., Modrek, A. S., & Placantonakis, D. G. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00417 · Cited by 231 · see citing works
Turkalp, Z. T., Karamchandani, J., & Das, S. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2014.1205 · Cited by 222 · see citing works
IDH1 and IDH2 mutations as novel therapeutic targets: current perspectives
de Botton, S., Mondesir, J., Willekens, C., & Touat, M. (2016) · Journal of Blood Medicine · doi:10.2147/jbm.s70716 · Cited by 220 · see citing works
Oncometabolites in renal cancer
Yong, C., Stewart, G. D., & Frezza, C. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0210-z · Cited by 212 · see citing works
Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence
Turcan, Ş., Makarov, V., Taranda, J., Wang, Y., Fabius, A. W. M., Wu, W., Zheng, Y., El-Amine, N., Haddock, S., Nanjangud, G. J., et al. (2017) · Nature Genetics · doi:10.1038/s41588-017-0001-z · Cited by 213 · see citing works
Self-citationMolecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer
Clark, O., Yen, K. E., & Mellinghoff, I. K. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1333 · Cited by 205 · see citing works
Dang, L., & Su, S.-S. M. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-044732 · Cited by 204 · see citing works
Therapeutic targeting of tumor suppressor genes
Morris, L. G. T., & Chan, T. A.-T. (2014) · Cancer · doi:10.1002/cncr.29140 · Cited by 201 · see citing works
Self-citationDriver mutations of cancer epigenomes
Roy, D. M., Walsh, L. A., & Chan, T. A.-T. (2014) · Protein & Cell · doi:10.1007/s13238-014-0031-6 · Cited by 183 · see citing works
Self-citationWang, Y., Yang, J., Wild, A. T., Wu, W. H., Shah, R., Danussi, C., Riggins, G. J., Kannan, K., Sulman, E. P., Chan, T. A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08905-8 · Cited by 184 · see citing works
Self-citationMolenaar, R. J., Radivoyevitch, T., Maciejewski, J. P., Noorden, C. J. F. V., & Bleeker, F. E. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.05.004 · Cited by 181 · see citing works
Harnessing the potential of epigenetic therapy to target solid tumors
Ahuja, N., Easwaran, H., & Baylin, S. B. (2014) · Journal of Clinical Investigation · doi:10.1172/jci69736 · Cited by 163 · see citing works
Borodovsky, A., Salmasi, V., Turcan, Ş., Fabius, A. W. M., Baía, G. S., Eberhart, C. G., WEINGART, J. D., Gallia, G. L., Baylin, S. B., Chan, T. A.-T., et al. (2013) · Oncotarget · doi:10.18632/oncotarget.1408 · Cited by 156 · see citing works
Self-citationZhang, X., Rao, A., Sette, P., Deibert, C., Pomerantz, A., Kim, W. J., Kohanbash, G., Chang, Y., Park, Y., Engh, J. A., et al. (2016) · Neuro-Oncology · doi:10.1093/neuonc/now061 · Cited by 157 · see citing works
Self-citationIsocitrate dehydrogenase‐mutant glioma: Evolving clinical and therapeutic implications
Miller, J. J., Shih, H. A., Andronesi, O. C., & Cahill, D. P. (2017) · Cancer · doi:10.1002/cncr.31039 · Cited by 152 · see citing works
Andronesi, O. C., Loebel, F., Bogner, W., Marjańska, M., Heiden, M. G. V., Iafrate, A. J., Dietrich, J., Batchelor, T. T., Gerstner, E. R., Kaelin, W. G., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0656 · Cited by 153 · see citing works
The Transcriptional and Epigenetic Landscape of Cancer Cell Lineage Plasticity
Davies, A., Zoubeidi, A., Beltran, H., & Selth, L. A. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0225 · Cited by 155 · see citing works
Oncometabolites‐driven tumorigenesis: From genetics to targeted therapy
Morin, A., Letouzé, É., Gimenez‐Roqueplo, A., & Favier, J. (2014) · International Journal of Cancer · doi:10.1002/ijc.29080 · Cited by 150 · see citing works
Oncogenic Activities of IDH1/2 Mutations: From Epigenetics to Cellular Signaling
Gagné, L. M., Boulay, K., Topisirović, I., Huot, M., & Mallette, F. A. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.06.002 · Cited by 141 · see citing works
Methylation across the central dogma in health and diseases: new therapeutic strategies
Liu, R., Zhao, E., Yu, H., Yuan, C., Abbas, M. N., & Cui, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01528-y · Cited by 147 · see citing works
Valente, S., Liu, Y., Schnekenburger, M., Zwergel, C., Cosconati, S., Gros, C., Tardugno, M., Labella, D., Florean, C., Minden, S., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm4012627 · Cited by 138 · see citing works
Metabolism and Epigenetic Interplay in Cancer: Regulation and Putative Therapeutic Targets
Miranda‐Gonçalves, V., Lameirinhas, A., Henrique, R., & Jerónimo, C. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00427 · Cited by 122 · see citing works
Epigenetic Targeting of Glioblastoma
Romani, M., Pistillo, M. P., & Banelli, B. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00448 · Cited by 115 · see citing works
Wang, Y., Wild, A. T., Turcan, Ş., Wu, W., Sigel, C., Klimstra, D. S., Ma, X., Gong, Y., Holland, E. C., Huse, J. T., et al. (2020) · Science Advances · doi:10.1126/sciadv.aaz3221 · Cited by 109 · see citing works
Self-citationIDH inhibition in gliomas: from preclinical models to clinical trials
Rudà, R., Horbinski, C., van den Bent, M. J., Preusser, M., & Soffietti, R. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-00967-7 · Cited by 104 · see citing works
The Role of piRNA and its Potential Clinical Implications in Cancer
Assumpção, C. B., Calcagno, D. Q., Araújo, T. M. T., dos Santos, S. E. B., dos Santos, Â. K. C. R., Riggins, G. J., Burbano, R. M. R., & de Assumpção, P. P. (2015) · Epigenomics · doi:10.2217/epi.15.37 · Cited by 98 · see citing works
Self-citationDewdney, B., Jenkins, M. R., Best, S. A., Freytag, S., Prasad, K., Holst, J., Endersby, R., & Johns, T. G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01637-8 · Cited by 100 · see citing works
5-Hydroxymethylcytosine: An epigenetic mark frequently deregulated in cancer
Kroeze, L. I., van der Reijden, B. A., & Jansen, J. H. (2015) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2015.01.001 · Cited by 95 · see citing works
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 91 · see citing works
Gailhouste, L., Liew, L. C., Hatada, I., Nakagama, H., & Ochiya, T. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0487-z · Cited by 90 · see citing works
Role of imaging in the era of precision medicine
Giardino, A., Gupta, S., Olson, E., Sepulveda, K., Lenchik, L., Ivanidze, J., Rakow-Penner, R., Patel, M. J., Subramaniam, R. M., & Ganeshan, D. (2017) · Academic Radiology · doi:10.1016/j.acra.2016.11.021 · Cited by 87 · see citing works
Context-dependent actions of Polycomb repressors in cancer
Koppens, M. A. J., & van Lohuizen, M. (2015) · Oncogene · doi:10.1038/onc.2015.195 · Cited by 86 · see citing works
Friend or foe—IDH1 mutations in glioma 10 years on
Huang, L. E. (2019) · Carcinogenesis · doi:10.1093/carcin/bgz134 · Cited by 82 · see citing works
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 83 · see citing works
DNA Methylation: From Cancer Biology to Clinical Perspectives
Chen, C., Wang, Z., Ding, Y., Wang, L., Wang, S., Wang, H., & Qin, Y. (2022) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2712326 · Cited by 83 · see citing works
Byron, S. A., Tran, N. L., Halperin, R. F., Phillips, J. J., Kuhn, J. G., de Groot, J. F., Colman, H., Ligon, K. L., Wen, P. Y., Cloughesy, T. F., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0963 · Cited by 80 · see citing works
Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma
Jalbert, L. E., Elkhaled, A., Phillips, J. J., Neill, E., Williams, A. A., Crane, J. C., Olson, M. P., Molinaro, A. M., Berger, M. S., Kurhanewicz, J. V., et al. (2017) · Scientific Reports · doi:10.1038/srep44792 · Cited by 79 · see citing works
Emadi, A., Faramand, R. G., Carter‐Cooper, B., Tolu, S. S., Ford, L. A., Lapidus, R. G., Wetzler, M., Wang, E. S., Etemadi, A., & Griffiths, E. A. (2015) · American Journal of Hematology · doi:10.1002/ajh.23965 · Cited by 78 · see citing works
Differentiation Therapy by Epigenetic Reconditioning Exerts Antitumor Effects on Liver Cancer Cells
Gailhouste, L., Liew, L. C., Yasukawa, K., Hatada, I., Tanaka, Y., Nakagama, H., & Ochiya, T. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.04.018 · Cited by 77 · see citing works
PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma
Fons, N. R., Sundaram, R. K., Breuer, G. A., Peng, S., McLean, R. L., Kalathil, A., Schmidt, M. S., Carvalho, D. M., Mackay, A. G., Jones, C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11732-6 · Cited by 77 · see citing works
Yamashita, A. S., Rosa, M. D. C., Borodovsky, A., Festuccia, W. T., Chan, T. A.-T., & Riggins, G. J. (2018) · Neuro-Oncology · doi:10.1093/neuonc/noy146 · Cited by 73 · see citing works
Self-citationVastrad, B. M., Vastrad, C. M., Godavarthi, A., & Hariharapura, R. C. (2017) · Medical Oncology · doi:10.1007/s12032-017-1043-x · Cited by 72 · see citing works
Epigenetic Therapy for Solid Tumors: from Bench Science to Clinical Trials
Juo, Y.-Y., Gong, X.-J., Mishra, A., Cui, X. X., Baylin, S. B., Azad, N. S., & Ahuja, N. (2015) · Epigenomics · doi:10.2217/epi.14.73 · Cited by 71 · see citing works
Miller, J. J. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01238-3 · Cited by 69 · see citing works
Potential New Therapies for Pediatric Diffuse Intrinsic Pontine Glioma
Long, W., Yang, Y., Chen, S., Cao, Q., Zhao, W., & Liu, Q. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00495 · Cited by 66 · see citing works
Leather, T., Jenkinson, M. D., Das, K., & Poptani, H. (2017) · Metabolites · doi:10.3390/metabo7020029 · Cited by 65 · see citing works
Mito, J. K., Bishop, J. A., Sadow, P. M., Stelow, E. B., Faquin, W. C., Mills, S. E., Krane, J. F., French, C. A., Fletcher, C. D. �., Hornick, J. L., et al. (2018) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000001064 · Cited by 64 · see citing works
Hu, J. L., Western, S., & Kesari, S. (2016) · Frontiers in Oncology · doi:10.3389/fonc.2016.00180 · Cited by 64 · see citing works
Metabolic Dysregulations and Epigenetics: A Bidirectional Interplay that Drives Tumor Progression
Crispo, F., Condelli, V., Lepore, S., Notarangelo, T., Sgambato, A., Esposito, F., Maddalena, F., & Landriscina, M. (2019) · Cells · doi:10.3390/cells8080798 · Cited by 61 · see citing works
Isocitrate Dehydrogenase Mutations in Glioma: Genetics, Biochemistry, and Clinical Indications
Liu, Y., Lang, F., Chou, F.-J., Zaghloul, K. A., & Yang, C. (2020) · Biomedicines · doi:10.3390/biomedicines8090294 · Cited by 61 · see citing works
Dynamic reprogramming of DNA methylation in SETD2-deregulated renal cell carcinoma
Tiedemann, R. L., Hlady, R. A., Hanavan, P. D., Lake, D. F., Tibes, R., Lee, J., Choi, J.-H., Ho, T. H., & Robertson, K. D. (2015) · Oncotarget · doi:10.18632/oncotarget.6481 · Cited by 63 · see citing works
Riobello, C., López‐Hernández, A., Cabal, V. N., García‐Marín, R., Suárez–Fernández, L., Sánchez‐Fernández, P., Vivanco, B., Blanco, V., López, F., Franchi, A., et al. (2019) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000001420 · Cited by 61 · see citing works
Mutated Chromatin Regulatory Factors as Tumor Drivers in Cancer
Koschmann, C. J., Núñez, F. J., Mendez, F., Brosnan‐Cashman, J. A., Meeker, A. K., Lowenstein, P. R., & Castro, M. G. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2301 · Cited by 59 · see citing works
Oncometabolic mutation IDH1 R132H confers a metformin-hypersensitive phenotype
Cuyàs, E., Fernández‐Arroyo, S., Corominas-Faja, B., Rodríguez‐Gallego, E., Bosch‐Barrera, J., Martı́n-Castillo, B., Llorens, R., Joven, J., & Menéndez, J. A. (2015) · Oncotarget · doi:10.18632/oncotarget.3733 · Cited by 58 · see citing works
The Warburg effect: a balance of flux analysis
Vaitheesvaran, B., Xu, J., Yee, J. K., Lu, Q., Go, V. L. W., Xiao, G. G., & Lee, W. N. (2014) · Metabolomics · doi:10.1007/s11306-014-0760-9 · Cited by 58 · see citing works
Connections between metabolism and epigenetics: mechanisms and novel anti-cancer strategy
Chen, C., Wang, Z., & Qin, Y. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.935536 · Cited by 60 · see citing works
Progress in the application of molecular biomarkers in gliomas
Wang, J., Su, H.-K., Zhao, H., Chen, Z.-P., & To, S. S. T. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.07.148 · Cited by 57 · see citing works
Mutant IDH in Gliomas: Role in Cancer and Treatment Options
Solomou, G., Finch, A., Asghar, A., & Bardella, C. (2023) · Cancers · doi:10.3390/cancers15112883 · Cited by 57 · see citing works
The clinical use of IDH1 and IDH2 mutations in gliomas
Pïcca, A., Berzero, G., Stefano, A. L. D., & Sanson, M. (2018) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2018.1548935 · Cited by 55 · see citing works
Ozair, A., Bhat, V., Alisch, R. S., Khosla, A. A., Kotecha, R. R., Odia, Y., McDermott, M. W., & Ahluwalia, M. S. (2023) · Cancers · doi:10.3390/cancers15041342 · Cited by 51 · see citing works
Therapies for IDH-Mutant Gliomas
Nasany, R. A., & de la Fuente, M. I. (2023) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-023-01265-3 · Cited by 50 · see citing works
Xu, Y., Li, P., Liu, Y., Xin, D., Lei, W., Liang, A., Han, W., & Qian, W. (2022) · 癌症：英文版 · doi:10.1002/cac2.12313 · Cited by 45 · see citing works
A new sensitive PCR assay for one-step detection of 12 IDH1/2 mutations in glioma
Catteau, A., Girardi, H., Monville, F., Poggionovo, C., Carpentier, S., Frayssinet, V., Voss, J. S., Jenkins, R. B., Boisselier, B., Mokhtari, K., et al. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-58 · Cited by 46 · see citing works
Madala, H. R., Punganuru, S. R., Arutla, V., Misra, S., Thomas, T., & Srivenugopal, K. S. (2018) · Cancers · doi:10.3390/cancers10020049 · Cited by 46 · see citing works
Characterization of systemic immunosuppression by IDH mutant glioma small extracellular vesicles
Ludwig, N., Rao, A., Sandlesh, P., Yerneni, S. S., Swain, A. D., Bullock, K. M., Hansen, K. M., Zhang, X., Jaman, E., Allen, J., et al. (2021) · Neuro-Oncology · doi:10.1093/neuonc/noab153 · Cited by 44 · see citing works
NAD Synthesis Pathway Interference Is a Viable Therapeutic Strategy for Chondrosarcoma
Peterse, E. F. P., van den Akker, B. E. W. M., Niessen, B., Oosting, J., Suijker, J., de Jong, Y., Danen, E. H. J., Cleton-Jansen, A., & Bovée, J. V. M. G. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-17-0293 · Cited by 43 · see citing works
Zhou, Z., Ibekwe, E., & Chornenkyy, Y. (2018) · Antioxidants · doi:10.3390/antiox7010016 · Cited by 43 · see citing works
Evolving cell states and oncogenic drivers during the progression of IDH-mutant gliomas
Wu, J., Castro, L. N. G., Battaglia, S., Farran, C. A. E., D’Antonio, J. P., Miller, T. E., Suvà, M. L., & Bernstein, B. (2024) · Nature Cancer · doi:10.1038/s43018-024-00865-3 · Cited by 41 · see citing works
Patties, I., Kallendrusch, S., Böhme, L., Kendzia, E., Oppermann, H., Gaunitz, F., Kortmann, R., & Glasow, A. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1434-2 · Cited by 42 · see citing works
Epigenetic dynamics in cancer stem cell dormancy
Ferrer, A. I., Trinidad, J. R., Sandiford, O. A., Etchegaray, J., & Rameshwar, P. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09882-x · Cited by 44 · see citing works
Gerometabolites: The pseudohypoxic aging side of cancer oncometabolites
Menéndez, J. A., Alarcón, T., & Joven, J. (2014) · Cell Cycle · doi:10.4161/cc.28079 · Cited by 41 · see citing works
IDH Inhibitors and Beyond: The Cornerstone of Targeted Glioma Treatment
Gatto, L., Franceschi, E., Tosoni, A., Nunno, V. D., Maggio, I., Lodi, R., & Brandes, A. A. (2021) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-021-00537-3 · Cited by 43 · see citing works
Contribution of the Wnt Pathway to Defining Biology of Glioblastoma
Tompa, M., Kálovits, F., Nagy, Á., & Kálmán, B. (2018) · NeuroMolecular Medicine · doi:10.1007/s12017-018-8514-x · Cited by 40 · see citing works
Beyond the Influence of IDH Mutations: Exploring Epigenetic Vulnerabilities in Chondrosarcoma
Venneker, S., Kruisselbrink, A. B., Baranski, Z., Palubeckaitė, I., Bruijn, I. H. B., Oosting, J., French, P. J., Danen, E. H. J., & Bovée, J. V. M. G. (2020) · Cancers · doi:10.3390/cancers12123589 · Cited by 39 · see citing works
Li, X., Lu, H., Fan, G., He, M., Sun, Y., Xu, K., & Shi, F.-J. (2017) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-017-2478-3 · Cited by 38 · see citing works
Tumor heterogeneity and tumor-microglia interactions in primary and recurrent IDH1-mutant gliomas
Blanco-Carmona, E., Narayanan, A., Hernandez, I., Nieto, J. C., Elosua-Bayés, M., Sun, X., Schmidt, C. S., Pamir, M. N., Özduman, K., Herold‐Mende, C. C., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101249 · Cited by 37 · see citing works
IGFBP2 expression predicts IDH-mutant glioma patient survival
Huang, L. E., Cohen, A. L., Colman, H., Jensen, R. L., Fults, D. W., & Couldwell, W. T. (2016) · Oncotarget · doi:10.18632/oncotarget.13329 · Cited by 37 · see citing works
From Laboratory Studies to Clinical Trials: Temozolomide Use in IDH-Mutant Gliomas
Sun, X., & Turcan, Ş. (2021) · Cells · doi:10.3390/cells10051225 · Cited by 37 · see citing works
- Authors
- Turcan, S., Fabius, A. W. M., Borodovsky, A., Pedraza, A., Brennan, C., Huse, J., Viale, A., Riggins, G. J., & Chan, T. A.
- Affiliations
- Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
- Memorial Sloan Kettering Cancer Center (US)
- Johns Hopkins University (US)
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2013-09-16
- Volume
- 4
- Issue
- 10
- Pages
- 1729-1736
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC3858559
- OpenAlex
- W2158900087
- Cited by
- 240
- References
- 21
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 8 · 2023: 22 · 2022: 18 · 2021: 20 · 2020: 12 · 2019: 21 · 2018: 24 · 2017: 26 · 2016: 27 · 2015: 16 · 2014: 24 · 2013: 1
- FWCI
- 11.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Sontag Foundation
- Memorial Sloan-Kettering Cancer Center
- National Institutes of Health (NIH T32, T32 grant)
- National Cancer Institute (T32CA160001, R01CA154767, R01CA177828, P30CA008748)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- IDH1 mutation, glioma, DNA methylation, DNMT inhibitors, glioma stem cells, differentiation, 2-hydroxyglutarate, G-CIMP, epigenetic reprogramming, stem cell-like properties, methylome, hypomethylating agents, gene expression reprogramming, tumor growth inhibition, IDH2
- MeSH terms
- Decitabine, Animals, Antimetabolites, Antineoplastic, Azacitidine, Brain Neoplasms, Cell Differentiation, DNA (Cytosine-5-)-Methyltransferases, Female, Glioma, Humans, Isocitrate Dehydrogenase, Mutation, Mice, SCID, DNA Methylation, Cell Growth Processes, Mice, Heterografts
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
