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
“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]
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]
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
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–300 of 1,001
Exploring the molecular interface between hypoxia-inducible factor signalling and mitochondria
Thomas, L. W., & Ashcroft, M. A. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03039-y · Cited by 219
Nacev, B. A., Jones, K. B., Intlekofer, A. M., Yu, J., Allis, C. D., Tap, W. D., Ladanyi, M., & Nielsen, T. O. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0288-4 · Cited by 214
Boscoe, A. N., Rolland, C., & Kelley, R. K. (2019) · Journal of Gastrointestinal Oncology · doi:10.21037/jgo.2019.03.10 · Cited by 210
Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML
Chaturvedi, A., Araujo Cruz, M. M., Jyotsana, N., Sharma, A., Yun, H., Görlich, K., Wichmann, M., Schwarzer, A., Preller, M., Thol, F., et al. (2013) · Blood · doi:10.1182/blood-2013-03-491571 · Cited by 210
Choe, S. E., Wang, H., Dinardo, C. D., Stein, E. M., de Botton, S., Roboz, G. J., Altman, J. K., Mims, A. S., Watts, J. M., Pollyea, D. A., et al. (2020) · Blood Advances · doi:10.1182/bloodadvances.2020001503 · Cited by 218
Molecular 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 210
Self-citationMolenaar, R. J., Verbaan, D., Lamba, S., Zanon, C., Jeuken, J. W. M., Boots‐Sprenger, S., Wesseling, P., Hulsebos, T. J. M., Troost, D., van Tilborg, A. A., et al. (2014) · Neuro-Oncology · doi:10.1093/neuonc/nou005 · Cited by 211
Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG in Vivo
Popovici-Müller, J. V., Saunders, J. O., Salituro, F. G., Travins, J. M., Yan, S., Zhao, F., Größ, S., Dang, L., Yen, K. E., Yang, H., et al. (2012) · ACS Medicinal Chemistry Letters · doi:10.1021/ml300225h · Cited by 204
Dang, L., & Su, S.-S. M. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-044732 · Cited by 204
Chung, C., Sweha, S. R., Pratt, D. W., Tamrazi, B., Panwalkar, P., Banda, A., Bayliss, J. M., Hawes, D., Yang, F., Lee, H., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.07.008 · Cited by 204
Ge, T., Gu, X., Jia, R., Ge, S., Chai, P., Zhuang, A., & Fan, X. (2022) · 癌症：英文版 · doi:10.1002/cac2.12374 · Cited by 220
TET proteins and 5‐methylcytosine oxidation in hematological cancers
Ko, M., An, J., Pastor, W. A., Koralov, S. B., Rajewsky, K., & Rao, A. (2014) · Immunological Reviews · doi:10.1111/imr.12239 · Cited by 202
Human Phosphoglycerate Dehydrogenase Produces the Oncometabolite d -2-Hydroxyglutarate
Fan, J., Teng, X., Liu, L., Mattaini, K. R., Looper, R., Heiden, M. G. V., & Rabinowitz, J. D. (2014) · ACS Chemical Biology · doi:10.1021/cb500683c · Cited by 206
Therapeutic targeting of tumor suppressor genes
Morris, L. G. T., & Chan, T. A.-T. (2014) · Cancer · doi:10.1002/cncr.29140 · Cited by 209
Self-citationCharacterizing DNA methylation alterations from The Cancer Genome Atlas
Weisenberger, D. J. (2014) · Journal of Clinical Investigation · doi:10.1172/jci69740 · Cited by 200
Revisiting the role of metabolism during development
Miyazawa, H., & Aulehla, A. (2018) · Development · doi:10.1242/dev.131110 · Cited by 196
Cytokine-like Roles for Metabolites in Immunity
Zasłona, Z., & O'Neill, L. A. J. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.04.002 · Cited by 202
Dinardo, C. D., PROPERT, K. J., Loren, A. W., Paietta, E. M., Sun, Z., Levine, R. L., Straley, K. S., Yen, K. E., Patel, J. P., Agresta, S. V., et al. (2013) · Blood · doi:10.1182/blood-2013-03-493197 · Cited by 210
Self-citationThe winding path of protein methylation research: milestones and new frontiers
Murn, J., & Shi, Y. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.35 · Cited by 205
Clonal heterogeneity of acute myeloid leukemia treated with the IDH2 inhibitor enasidenib
Quek, L. S., David, M. D., Kennedy, A., Metzner, M., Amatangelo, M. D., Shih, A. H., Stoilova, B., Quivoron, C., Heiblig, M., Willekens, C., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0115-6 · Cited by 199
Self-citationDysregulation of glutaminase and glutamine synthetase in cancer
Matés, J. M., Campos-Sandoval, J. A., Santos-Jiménez, J. D. L., & Márquez, J. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.09.011 · Cited by 197
Emerging therapeutic drugs for AML
Stein, E. M., & Tallman, M. S. (2015) · Blood · doi:10.1182/blood-2015-07-604538 · Cited by 195
Inoue, S., Li, W. Y., Tseng, A., Beerman, I., Elia, A., Bendall, S. C., Lemonnier, F., Kron, K. J., Cescon, D. W., Hao, Z., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.05.018 · Cited by 204
Self-citationTargeting pyrimidine synthesis accentuates molecular therapy response in glioblastoma stem cells
Wang, X., Yang, K., Wu, Q., Kim, L. J. Y., Morton, A. R., Gimple, R. C., Prager, B. C., Shi, Y., Zhou, W., Bhargava, S., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aau4972 · Cited by 197
ATRX and DAXX: Mechanisms and MutationsPreprint
Dyer, M. A., Qadeer, Z. A., Valle‐García, D., & Bernstein, E. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026567 · Cited by 208
Delgado-Martín, B., & Medina, M. Á. (2020) · Advanced Science · doi:10.1002/advs.201902971 · Cited by 198
Janke, R., Dodson, A. E., & Rine, J. (2015) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100814-125544 · Cited by 199
Leu, S., von Felten, S., Frank, S., Vassella, E., Vajtai, I., Taylor, E., Schulz, M., Hütter, G., Hench, J., Schucht, P., et al. (2013) · Neuro-Oncology · doi:10.1093/neuonc/nos317 · Cited by 191
The emerging role of fumarate as an oncometabolite
Yang, M., Soga, T., Pollard, P. J., & Adam, J. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00085 · Cited by 189
Driver 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 188
Self-citationExome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas
Zhang, L., Chen, L. H., Wan, H., Yang, R. R., Wang, Z., Feng, J., Yang, S., Jones, S., Wang, S., Zhou, W., et al. (2014) · Nature Genetics · doi:10.1038/ng.2995 · Cited by 188
The CpG Island Methylator Phenotype: What's in a Name?
Hughes, L., Melotte, V., Schrijver, J. M. D., de Maat, M., Smit, V. T. H. B. M., Bovée, J. V. M. G., French, P. J., van den Brandt, P. A., Schouten, L. J., Meyer, T. D., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4306 · Cited by 182
Long-Term Survival in Primary Glioblastoma With Versus Without Isocitrate Dehydrogenase Mutations
Hartmann, C. J., Hentschel, B., Simon, M., Westphal, M., Schackert, G., Tonn, J. C., Loeffler, M., Reifenberger, G., Pietsch, T., von Deimling, A., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0017 · Cited by 186
Cancer stem cell metabolism: target for cancer therapy
Chae, Y. C., & Kim, J. H. (2018) · BMB Reports · doi:10.5483/bmbrep.2018.51.7.112 · Cited by 185
Metabolic stress regulates cytoskeletal dynamics and metastasis of cancer cells
Caino, M. C., Chae, Y. C., Vaira, V., Ferrero, S., Nosotti, M., Martin, N., Weeraratna, A. T., O’Connell, M. P., Jernigan, D. L., Fatatis, A., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67841 · Cited by 184
Aldape, K., Amin, S. B., Ashley, D. M., Barnholtz‐Sloan, J. S., Bates, A. J., Beroukhim, R., Bock, C., Brat, D. J., Claus, E. B., Costello, J., et al. (2018) · Neuro-Oncology · doi:10.1093/neuonc/noy020 · Cited by 179
Metabolic Plasticity in Chemotherapy Resistance
Desbats, M. A., Giacomini, I., Prayer‐Galetti, T., & Montopoli, M. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00281 · Cited by 190
Chen, C., Liu, Y., Lü, C., Cross, J. R., Morris, J. P., Shroff, A., Ward, P. S., Bradner, J. E., Thompson, C. B., & Lowe, S. W. (2013) · Genes & Development · doi:10.1101/gad.226613.113 · Cited by 186
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 186
Ward, P. S., Lü, C., Cross, J. R., Abdel-Wahab, O. I., Levine, R. L., Schwartz, G. K., & Thompson, C. B. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.435495 · Cited by 188
Self-citationNew IDH1 mutant inhibitors for treatment of acute myeloid leukemia
Okoye-Okafor, U. C., Bartholdy, B., Cartier, J., Gao, E. N., Pietrak, B., Rendina, A. R., Rominger, C., Quinn, C., Smallwood, A., Wiggall, K. J., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1930 · Cited by 180
The oncometabolite 2-hydroxyglutarate activates the mTOR signalling pathway
Carbonneau, M., M. Gagné, L., Lalonde, M.-E., Germain, M.-A., Motorina, A., Guiot, M.-C., Secco, B., Vincent, E. E., Tumber, A., Hulea, L., et al. (2016) · Nature Communications · doi:10.1038/ncomms12700 · Cited by 180
Up-regulation of glycolytic metabolism is required for HIF1α-driven bone formation
Regan, J. N., Lim, J., Shi, Y., Joeng, K. S., Arbeit, J. M., Shohet, R. V., & Long, F. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1324290111 · Cited by 184
Zhai, L., Ladomersky, E., Lauing, K. L., Wu, M., GENET, M. D., Gritsina, G., Győrffy, B., Brastianos, P. K., Binder, D. C., Sosman, J. A., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0120 · Cited by 182
Oncometabolites: Unconventional triggers of oncogenic signalling cascades
Sciacovelli, M., & Frezza, C. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.025 · Cited by 184
The Metabolic Impact on Histone Acetylation and Transcription in Ageing
Peleg, S., Feller, C., Ladurner, A. G., & Imhof, A. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.05.008 · Cited by 178
Dinardo, C. D., Stein, A. S., Stein, E. M., Fathi, A. T., Frankfurt, O., Schuh, A. C., Döhner, H., Martinelli, G., Patel, P. A., Raffoux, E., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.20.01632 · Cited by 180
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 183
Cancer Stem Cell Immunology: Key to Understanding Tumorigenesis and Tumor Immune Escape?
Bruttel, V. S., & Wischhusen, J. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00360 · Cited by 177
Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate
Andronesi, O. C., Rapalino, O., Gerstner, E. R., Chi, A. S., Batchelor, T. T., Cahill, D. P., Sorensen, A. G., & Rosen, B. R. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67229 · Cited by 178
Greater Than the Sum of Parts: Complexity of the Dynamic Epigenome
Soshnev, A. A., Josefowicz, S. Z., & Allis, C. D. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.004 · Cited by 181
Diffuse Infiltrating Oligodendroglioma and Astrocytoma
van den Bent, M. J., Smits, M., Kros, J. M., & Chang, S. M. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.72.6737 · Cited by 184
Metabolic changes in cancer: beyond the Warburg effect
Wu, W., & Zhao, S. (2013) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gms104 · Cited by 173
A landscape of metabolic variation across tumor types
Reznik, E., Luna, A., Aksoy, B. A., Liu, E. M., La, K., Ostrovnaya, I., Creighton, C. J., Hakimi, A. A., & Sander, C. (2018) · Cell Systems · doi:10.1016/j.cels.2017.12.014 · Cited by 172
Mutant IDH1 and thrombosis in gliomas
Unruh, D. J., Schwarze, S. R., Khoury, L., Thomas, C., Wu, M., Chen, L., Chen, R., Liu, Y., Schwartz, M. A., Amidei, C., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1620-7 · Cited by 173
Sex Differences in Intestinal Carbohydrate Metabolism Promote Food Intake and Sperm Maturation
Hudry, B., de Goeij, E., Mineo, A., Gaspar, P., Hadjieconomou, D., Studd, C., Mokochinski, J. B., Kramer, H., Plaçais, P.-Y., Préat, T., et al. (2019) · Cell · doi:10.1016/j.cell.2019.07.029 · Cited by 164
Tommasini-Ghelfi, S., Murnan, K., Kouri, F. M., Mahajan, A., May, J., & Stegh, A. H. (2019) · Science Advances · doi:10.1126/sciadv.aaw4543 · Cited by 166
HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells
Lee, S.-H., Golinska, M., & Griffiths, J. R. (2021) · Cells · doi:10.3390/cells10092371 · Cited by 169
Personalized treatment strategies in glioblastoma: MGMT promoter methylation status
Thon, N., Kreth, S., & Kreth, F. W. (2013) · OncoTargets and Therapy · doi:10.2147/ott.s50208 · Cited by 180
Control of YAP/TAZ Activity by Metabolic and Nutrient-Sensing Pathways
Santinon, G., Pocaterra, A., & Dupont, S. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.11.004 · Cited by 169
Anticancer Agents That Counteract Tumor Glycolysis
Granchi, C., & Minutolo, F. (2012) · ChemMedChem · doi:10.1002/cmdc.201200176 · Cited by 167
What do we know about IDH1/2 mutations so far, and how do we use it?
Horbinski, C. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1106-9 · Cited by 169
Metabolic coordination of cell fate by α-ketoglutarate-dependent dioxygenases
Baksh, S. C., & Finley, L. W. S. (2021) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.09.010 · Cited by 165
Advances in understanding of angioimmunoblastic T-cell lymphoma
Chiba, S., & Sakata‐Yanagimoto, M. (2020) · Leukemia · doi:10.1038/s41375-020-0990-y · Cited by 167
Insights Into the Pathogenesis of Sweet's Syndrome
Heath, M. S., & Ortega‐Loayza, A. G. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00414 · Cited by 162
Caravella, J. A., Lin, J., Diebold, R. B., Campbell, A.-M., Ericsson, A. M., Gustafson, G. R., Wang, Z., Castro, J., Clarke, A., Gotur, D., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01423 · Cited by 162
Zhang, P., Qin, X., Liu, L., Li, S., & Dong, L. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.562798 · Cited by 169
The mutational landscape of phosphorylation signaling in cancer
Reimand, J., Wagih, O., & Bader, G. D. (2013) · Scientific Reports · doi:10.1038/srep02651 · Cited by 163
Epigenetic modifications by dietary phytochemicals: Implications for personalized nutrition
Shankar, S., Kumar, D., & Srivastava, R. K. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.11.002 · Cited by 164
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 165
Myeloproliferative neoplasms: from origins to outcomes
Nangalia, J., & Green, A. R. (2017) · Blood · doi:10.1182/blood-2017-06-782037 · Cited by 167
KDM4C and ATF4 Cooperate in Transcriptional Control of Amino Acid Metabolism
Zhao, E., Ding, J., Xia, Y., Liu, M., Ye, B., Choi, J.-H., Yan, C., Dong, Z., Huang, S., Zha, Y., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.053 · Cited by 165
Saha, S. K., Gordan, J. D., Kleinstiver, B. P., Vu, P., Najem, M. S., Yeo, J.-C., Shi, L., Kato, Y., Levin, R. S., Webber, J. T., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1442 · Cited by 160
Metabolic remodelling during early mouse embryo development
Zhao, J., Yao, K., Yu, H., Zhang, L., Xu, Y., Chen, L., Sun, Z., Zhu, Y., Zhang, C., Qian, Y., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00464-x · Cited by 167
Metabolic consequences of oncogenic IDH mutations
Parker, S. J., & Metallo, C. M. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.05.003 · Cited by 162
Pharmacogenomic Biomarkers for Improved Drug Therapy—Recent Progress and Future Developments
Lauschke, V. M., Milani, L. A., & Ingelman‐Sundberg, M. (2017) · The AAPS Journal · doi:10.1208/s12248-017-0161-x · Cited by 166
Classification of adult‐type diffuse gliomas: Impact of the World Health Organization 2021 update
Whitfield, B. T., & Huse, J. T. (2022) · Brain Pathology · doi:10.1111/bpa.13062 · Cited by 172
Induction of sarcomas by mutant IDH2Preprint
Lü, C., Venneti, S., Akalin, A., Fang, F., Ward, P. S., Dematteo, R. G., Intlekofer, A. M., Chen, C., Ye, J., Hameed, M., et al. (2013) · Genes & Development · doi:10.1101/gad.226753.113 · Cited by 162
Self-citationBorodovsky, 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 158
Self-citationWu, M., Shi, L., Dubrot, J., Merritt, J., Vijay, V., Wei, T.-Y., Kessler, E., Olander, K. E., Adil, R., Pankaj, A., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1077 · Cited by 158
Zhang, 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 161
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 154
The Roles of 2-Hydroxyglutarate
Du, X., & Hu, H. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.651317 · Cited by 160
The methyltransferase G9a regulates HoxA9-dependent transcription in AMLPreprint
Lehnertz, B., Pabst, C., Yi, L.-Y., Miller, M., Liu, F., Yi, L., Zhang, R., Krošl, J., Yung, E., Kirschner, J., et al. (2014) · Genes & Development · doi:10.1101/gad.236794.113 · Cited by 156
Teicher, B. A., Linehan, W. M., & Helman, L. J. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2587 · Cited by 152
Glioblastoma Stem-Like Cells, Metabolic Strategy to Kill a Challenging Target
Garnier, D., Renoult, O., Alves‐Guerra, M., Paris, F., & Pecqueur, C. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00118 · Cited by 161
Song, Y., Wu, F., & Wu, J. (2016) · Journal of Hematology & Oncology · doi:10.1186/s13045-016-0279-9 · Cited by 154
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 162
Bardella, C., Al‐Dalahmah, O., Krell, D., Brazauskas, P., Al‐Qahtani, K., Tomková, M., Adam, J., Serres, S., Lockstone, H. E., Freeman-Mills, L., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.08.017 · Cited by 157
Isocitrate Dehydrogenase Mutations in Glioma: From Basic Discovery to Therapeutics Development
Huang, J., Yu, J., Tu, L., Huang, N., Li, H., & Luo, Y. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00506 · Cited by 147
Metabolic Abnormalities in Glioblastoma and Metabolic Strategies to Overcome Treatment Resistance
Zhou, W., & Wahl, D. R. (2019) · Cancers · doi:10.3390/cancers11091231 · Cited by 152
A clinical perspective on the 2016 WHO brain tumor classification and routine molecular diagnostics
van den Bent, M. J., Weller, M., Wen, P. Y., Kros, J. M., Aldape, K. D., & Chang, S. M. (2017) · Neuro-Oncology · doi:10.1093/neuonc/now277 · Cited by 156
The molecular feature of macrophages in tumor immune microenvironment of glioma patients
Zhang, H., Luo, Y., Wu, W., Zhang, L., Wang, Z., Dai, Z., Feng, S., Cao, H., Cheng, Q., & Liu, Z. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.08.019 · Cited by 150
Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China
Wang, J.-H., Chen, W., Li, J., Wu, S., Chen, T., Zhu, Y., Zhang, W., Li, Y., Qiu, Y.-P., Zhao, A.-H., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315558110 · Cited by 146
Breathing-in epigenetic change with vitamin C
Monfort, A., & Wutz, A. (2013) · The EMBO Reports · doi:10.1038/embor.2013.29 · Cited by 140
Oncometabolites: tailoring our genes
Nowicki, S., & Gottlieb, E. (2015) · FEBS Journal · doi:10.1111/febs.13295 · Cited by 148
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 143
Andronesi, O. C., Arrillaga‐Romany, I., Ly, I., Bogner, W., Ratai, E., Reitz, K., Iafrate, A. J., Dietrich, J., Gerstner, E. R., Chi, A. S., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03905-6 · Cited by 141
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 155
Nutrient-sensing pathways and metabolic regulation in stem cells
Ochocki, J. D., & Simon, M. C. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201303110 · Cited by 140
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
