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Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome
Open accessAbstract
Point mutations of the NADP + -dependent isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) occur early in the pathogenesis of gliomas. When mutated, IDH1 and IDH2 gain the ability to produce the metabolite ( R )-2-hydroxyglutarate (2HG), but the downstream effects of mutant IDH1 and IDH2 proteins or of 2HG on cellular metabolism are unknown. We profiled >200 metabolites in human oligodendroglioma (HOG) cells to determine the effects of expression of IDH1 and IDH2 mutants. Levels of amino acids, glutathione metabolites, choline derivatives, and tricarboxylic acid (TCA) cycle intermediates were altered in mutant IDH1- and IDH2-expressing cells. These changes were similar to those identified after treatment of the cells with 2HG. Remarkably, N -acetyl-aspartyl-glutamate (NAAG), a common dipeptide in brain, was 50-fold reduced in cells expressing IDH1 mutants and 8.3-fold reduced in cells expressing IDH2 mutants. NAAG also was significantly lower in human glioma tissues containing IDH mutations than in gliomas without such mutations. These metabolic changes provide clues to the pathogenesis of tumors associated with IDH gene mutations.
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“a portion of the succinate that accumulates during ischemia and inflammation is released from the cell into the extracellular environment through poorly defined processes. This occurs following IR injury158,159, inflammation10, or cold exposure160.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [159]
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“These have been reported in mutant IDH1expressing cell models, ex vivo tumor samples, and in vivo patient studies, and include significant changes in choline-containing metabolites, N-acetyl aspartate, and glutamate (12-15).”
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“Cell Culture A previously characterized human anaplastic oligodendroglioma (HOG) was used for all studies, unless otherwise stated, kindly donated by Professor Hai Yan (Reitman et al., 2011).”
InfluentialGarrett, M. C., Sperry, J., Braas, D., Yan, W., Le, T. M., Mottahedeh, J., Ludwig, K., Eskin, A., Qin, Y., Levy, R., et al. (2018) · Cancer & Metabolism · doi:10.1186/s40170-018-0177-4 · Cited by 86
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“Isocitrate dehydrogenases (IDH) serve important roles in normal cell metabolism and growth (Figure 2) [18].”
BackgroundIDH1 R132H Mutation Generates a Distinct Phospholipid Metabolite Profile in Glioma
Esmaeili, M., Hamans, B. C., Navis, A. C., van Horssen, R., Bathen, T. F., Gribbestad, I. S., Leenders, W. P. J., & Heerschap, A. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0008 · Cited by 86
“An increased GPC level has been detected by mass spectrometry in oligodendroglioma cells expressing the IDH1 mutation as compared with wild-type cells (14), and a positive correlation of GPC with 2HG was found by HR-MAS of ex vivo Figure 5.”
Cystathionine as a marker for 1p/19q codeleted gliomas by in vivo magnetic resonance spectroscopy
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Metabolite sensing and signaling in cancer
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“ATP synthase (11), and by deregulating the tricarboxylic acid (TCA) cycle (12) in themitochondria.”
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“A recent report suggests a number of interesting additional changes in the metabolome of an IDH1/2 mutationcarrying human oligodendroglioma cell line, including various amino acids, glutathione metabolites, choline derivatives, and tricarboxylic acid cycle intermediates [30].”
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Metabolic Reprogramming in Mutant IDH1 Glioma Cells
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“[11] who investigated a genetically engineered human oligodendroglioma cell model using MS and a metabolomics approach.”
BackgroundMethodResultAmide proton transfer imaging might predict survival and IDH mutation status in high-grade glioma
Joo, B., Han, K., Ahn, S. S., Choi, Y. S., Chang, J. H., Kang, S., Kim, S. H., Zhou, J., & Lee, S. (2019) · European Radiology · doi:10.1007/s00330-019-06203-x · Cited by 80
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“likewise, nonesterified 2-Hg has been shown to produce metabolic changes comparable to those achieved by overexpression of r132H IDH1 in vitro [32].”
The comparison of clinical and biological characteristics between IDH1 and IDH2 mutations in gliomas
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“This finding corroborates that of a previous study [22, 23].”
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CD47 Receptor Globally Regulates Metabolic Pathways That Control Resistance to Ionizing Radiation
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“Metabolite Analysis—Metabolomic profiling analysis was performed by Metabolon as previously described (26, 27).”
BackgroundMethodMutations in the Isocitrate Dehydrogenase Genes IDH1 and IDH2 in Tumors
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“through attenuating the anti-oxidant system [63].”
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“This can occur through inactivation of components of the tricarboxylic acid (TCA) cycle and electron transport chain (ETC) (1-5).”
BackgroundLiubinas, S. V., D’Abaco, G. M., Moffat, B. A., Gonzales, M. F., Feleppa, F., Nowell, C. J., Gorelik, A., Drummond, K. J., O'Brien, T. J., Kaye, A. H., et al. (2014) · Epilepsia · doi:10.1111/epi.12662 · Cited by 76
“However, metabolic profiling of changes in human oligodendroglioma cells harboring IDH1/2mutations found lower levels of glutamate, most likely due to depletion during its conversion to a-ketoglutarate and then 2HG.(31) It has also been reported that low grade gliomas, especially those with loss of heterozygosity of 1…”
BackgroundLinks between cancer metabolism and cisplatin resistance
Cocetta, V., Ragazzi, E., & Montopoli, M. (2020) · International review of cytology · doi:10.1016/bs.ircmb.2020.01.005 · Cited by 77
Zhou, L., Wang, Z., Hu, C., Zhang, C., Kovatcheva‐Datchary, P., Yu, D., Liu, S., Ren, F., Wang, X., Li, Y., et al. (2018) · Journal of Proteome Research · doi:10.1021/acs.jproteome.8b00663 · Cited by 73
The Tricarboxylic Acid Cycle at the Crossroad Between Cancer and Immunity
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“By profiling the effect of oncogenic mutations in IDH1 and IDH2 genes on cellular metabolome, it was shown that IDH-mutant cells produce lower levels of branched-chain a -ketoacids (BCKAs) compared with IDH-normal cells (91).”
Mitochondrial Citrate Transporter-dependent Metabolic Signature in the 22q11.2 Deletion Syndrome
Napoli, E., Tassone, F., Wong, S., Angkustsiri, K., Simon, T. J., Song, G., & Giulivi, C. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.672360 · Cited by 71
“These compounds are metabolic intermediates in reactions catalyzed by malate dehydrogenase and hydroxyacid-oxoacid transhydrogenase (53, 54), and accumulation of 2HG affects some metabolic processes, such as the TCA cycle and branched-chain amino acid metabolism (55, 56).”
El-Habr, E. A., Dubois, L. G., Burel‐Vandenbos, F., Bogeas, A., Lipecka, J., Turchi, L., Lejeune, F., Coehlo, P. L. C., Yamaki, T., Wittmann, B. M., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1659-5 · Cited by 79
“(Durham, NC, USA) as previously described [45].”
Gadde, U. D., Oh, S., Lillehoj, H. S., & Lillehoj, E. P. (2018) · Scientific Reports · doi:10.1038/s41598-018-22004-6 · Cited by 80
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“Metabolite analysis Nontargeted metabolomic profiling analysis was performed by Metabolon as previously described (10).”
MethodMoreno, P., Jiménez‐Jiménez, C., Garrido‐Rodríguez, M., Calderón-Santiago, M., Molina, S., Lara‐Chica, M., Priego‐Capote, F., Salvatierra, Á., Muñóz, E., & Calzado, M. A. (2018) · Molecular Oncology · doi:10.1002/1878-0261.12369 · Cited by 71
“Metabolomic profiling analysis was performed by Metabolon as previously described (Reitman et al., 2011).”
MethodBiology of IDH mutant cholangiocarcinoma
Wu, M., Shi, L., Merritt, J., Zhu, A. X., & Bardeesy, N. M. (2022) · Hepatology · doi:10.1002/hep.32424 · Cited by 71
“(R)2HG can directly or indirectly cause other changes in overall cellular metabolism, including suppressing mitochondrial respiration by compromising the activity of cytochrome c oxidase,[22] depleting NAD+,[72– 74] down- regulating lipid synthesis,[73,75] lowering glycolysis,[76] and stimulating proline and glutamine…”
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Altered cancer cell metabolism in gliomas with mutant IDH1 or IDH2
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“Metabolomics, or global metabolite profiling, which is a new technology of functional genomics, can be used for investigating metabolite changes associated with some gene mutations [4].”
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“…a broad and unusual reprogramming of cellular metabolism (Chesnelong et al., 2014; Elkhaled et al., 2014; Esmaeili et al., 2014; Grassian et al., 2014; Izquierdo-Garcia et al., 2014; Izquierdo-Garcia et al., 2015b; Ohka et al., 2014; Reitman et al., 2014; Reitman et al., 2011; Tonjes et al., 2013).”
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“Whereas increased NAA levels exemplify CD, levels of both NAA and NAAG are decreased in glioma tumors (19, 20) coincident with decreased ASPA expression.”
BackgroundHuR is a post-transcriptional regulator of core metabolic enzymes in pancreatic cancer
Burkhart, R. A., Pineda, D. M., Chand, S. N., Romeo, C., Londin, E. R., Karoly, E. D., Cozzitorto, J. A., Rigoutsos, I., Yeo, C. J., Brody, J. R., et al. (2013) · RNA Biology · doi:10.4161/rna.25274 · Cited by 64
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Mitochondrial Retrograde Signalling and Metabolic Alterations in the Tumour Microenvironment
Yang, D., & Kim, J. (2019) · Cells · doi:10.3390/cells8030275 · Cited by 67
“2HG also inhibits the enzymatic activity of cytochrome c oxidase and ATP synthase [70,95] and alters the gene expression of TCA cycle enzymes in cancer cells [96].”
Enolase-1 is a therapeutic target in endometrial carcinoma
Zhao, M., Fang, W., Wang, Y., Guo, S., Shu, L., Wang, L., Chen, Y., Fu, Q., Liu, Y., Hua, S., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3639 · Cited by 65
“Further sample preparation, metabolic profiling, peak identification and curation were performed by Metabolon (Durham, NC, USA) using their described methods [53].”
MethodZhang, C., Bao, Z., Wang, H., Yan, W., Liu, Y., Li, M., Zhang, W., Chen, L., & Jiang, T. (2013) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-013-1519-9 · Cited by 64
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“Cho levels were found to be further elevated in mutan tumours when c mpared to WT, a measurement validated vi LC-MS, and a finding in line with previous studi s that have examined m tabolome-wide alterations seen in IDH mutated tumo rs [8,53].”
ResultBallester, L. Y., Lu, G., Zorofchian, S., Vantaku, V., Putluri, V., Yan, Y., Arevalo, O., Zhu, P., Riascos, R., Sreekumar, A., et al. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0588-z · Cited by 63
IDH Mutations in Tumorigenesis and Their Potential Role As Novel Therapeutic Targets
Krell, D., Mulholland, P. J., Frampton, A. E., Krell, J., Stebbing, J., & Bardella, C. (2013) · Future Oncology · doi:10.2217/fon.13.143 · Cited by 63
“(2013) 9(12) 1928 future science group IDH1 mutant cells shared multiple metabolic changes with 2HG-treated cells, but not with IDH1 wild-type knockdown cells, suggests that 2HG production is responsible for the metabolic effects observed [85].”
BackgroundInfluentialIsocitrate 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 62
“[72] profiled more than 200 metabolites in human oligodendroglioma cells in order to investigate metabolic reprogramming by the IDH1 mutant enzyme.”
BackgroundMetabolome 2.0: quantitative genetics and network biology of metabolic phenotypes
Dumas, M. (2012) · Molecular BioSystems · doi:10.1039/c2mb25167a · Cited by 63
Park, M. J., Aja, S., Li, Q., Degano, A. L., Penati, J., Zhuo, J., Roe, C. R., & Ronnett, G. V. (2014) · PLoS ONE · doi:10.1371/journal.pone.0109527 · Cited by 62
“Metabolomic profiling was performed by Metabolon as previously described in detail[81,82].”
MethodBaraibar, M. A., Hyzewicz, J., Rogowska-Wrzesińska, A., Bulteau, A., Prip‐Buus, C., Butler-Browne, G. S., & Friguet, B. (2016) · Aging · doi:10.18632/aging.101126 · Cited by 64
Sun, Y., Chen, B.-R., & Deshpande, A. J. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00041 · Cited by 64
“Proc Natl Acad Sci U S A (2014) 111(7):2548–53.”
BackgroundInfluentialDe novo synthesize of bile acids in pulmonary arterial hypertension lung
Zhao, Y. D., Yun, H., Peng, J., Yin, L., Chu, L., Wu, L., Michalek, R. D., Liu, M., Keshavjee, S. H., Waddell, T. K., et al. (2014) · Metabolomics · doi:10.1007/s11306-014-0653-y · Cited by 58
“Unbiased metabolomic profiling using liquid/gas chromatography coupled to mass spectrometry (LC/GC–MS) was performed as described (Reitman et al. 2011; Evans et al. 2009).”
Jenkins, Y., Sun, T., Markovtsov, V. V., Foretz, M., Li, W., Nguyen, H. N., Li, Y., Pan, A., Uy, G., Groß, L., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081870 · Cited by 57
“Frozen tissue and plasma samples were sent to Metabolon for unbiased metabolite analysis (Durham, NC) [27-29].”
MethodOncometabolic 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 60
“Our results confirm and expand earlier studies describing how metabolic reprogramming in mutant IDH1 cancer cells translates into changes on the cellular metabolome beyond the overproduction of the oncometabolite 2HG [88, 89].”
ResultNavis, A. C., Niclou, S. P., Fack, F., Stieber, D., van Lith, S. A. M., Verrijp, K. N., Wright, A. J., Stauber, J., Tops, B. B. J., Otte‐Höller, I., et al. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-18 · Cited by 61
“Indeed, glutathione levels appear to be lower in IDH1-mutated tumors [51].”
Matteo, D. A., Grunseth, A. J., Gonzalez, E. R., Anselmo, S. L., Kennedy, M. A., Moman, P., Scott, D. A., Hoang, A. D., & Sohl, C. D. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.776179 · Cited by 62
“The proposed oncometabolite D2HG alone can recapitulate tumorigenic phenotypes in cancer models (21, 22), but studies measuring global metabolomics changes between mutant IDH1 expression and D2HG treatment show some differences (23, 24), indicating loss of the This work was supported by National Institute of Health Gr…”
Metabolomics of colorectal cancer: past and current analytical platforms
Williams, M. D., Reeves, R., Resar, L. M. S., & Hill, H. H. (2013) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-013-6777-5 · Cited by 58
“For example, a global metabolomics study first uncovered the important role of 2-hydroxyglutarate (2-HG) in reprogramming cancer cells [105].”
Background5-Hydroxymethylcytosine Profiling as an Indicator of Cellular State
Laird, A., Thomson, J. P., Harrison, D. J., & Meehan, R. R. (2013) · Epigenomics · doi:10.2217/epi.13.69 · Cited by 58
Isocitrate dehydrogenase status and molecular subclasses of glioma and glioblastoma
Agnihotri, S., Aldape, K., & Zadeh, G. M. (2014) · Neurosurgical FOCUS · doi:10.3171/2014.9.focus14505 · Cited by 59
Metabolic adaptations in cancers expressing isocitrate dehydrogenase mutations
Hvinden, I. C., Cadoux-Hudson, T. A. D., Schofield, C. J., & McCullagh, J. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100469 · Cited by 63
“Changes in amino acid abundance have often been reported for mutIDH cell models, but as with the aforementioned metabolites, other than R-2-HG, the abundance changes are generally not consistent across studies or model types (Table 4),(102,104,106,107,114,116) with comprehensive analyses only being reported in a small…”
BackgroundResultInfluentialMutant 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 62
“Indeed, the production of D2-HG leads to significant reduction and drainage of TCA cycle substrates, and thus, carbohydrate sources [61,65].”
BackgroundMetabolomic Profile Predicts Development of Microalbuminuria in Individuals with Type 1 Diabetes
Haukka, J. K., Sandholm, N., Forsblom, C. M., Cobb, J. E., Groop, P., & Ferrannini, E. (2018) · Scientific Reports · doi:10.1038/s41598-018-32085-y · Cited by 54
Viswanath, P., Radoul, M., Izquierdo-García, J. L., Ong, W. Q., Luchman, H. A., Cairncross, J. G., Huang, B., Pieper, R. O., Phillips, J. J., & Ronen, S. M. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-2926 · Cited by 54
Antagonistic functional duality of cancer genes
Stepanenko, A. A., Vassetzky, Y. S., & KAVSAN, V. M. (2013) · Gene · doi:10.1016/j.gene.2013.07.047 · Cited by 54
A Novel Protein Protects Bacterial Iron-Dependent Metabolism from Nitric Oxide
Stern, A. M., Liu, B., Bakken, L. R., Shapleigh, J. P., & Zhu, J. (2013) · Journal of Bacteriology · doi:10.1128/jb.00836-13 · Cited by 54
Reversal of obesity-driven aggressiveness of endometrial cancer by metformin.
Guo, H., Kong, W., Zhang, L., Han, J., Clark, L. H., Yin, Y., Fang, Z., Sun, W., Wang, J., Gilliam, T. P., et al. (2019) · PubMed Central · Cited by 52
Gaster, M., Nehlin, J. O., & Minet, A. D. (2012) · Archives of Physiology and Biochemistry · doi:10.3109/13813455.2012.656653 · Cited by 55
Keenan, M. J., Martin, R. J., Raggio, A. M., McCutcheon, K. L., Brown, I. L., Birkett, A. M., Newman, S. S., Skaf, J. S., Hegsted, M., Tulley, R. T., et al. (2012) · Lifestyle Genomics · doi:10.1159/000335319 · Cited by 54
Metabolic Profiling, a Noninvasive Approach for the Detection of Experimental Colorectal Neoplasia
Montrose, D. C., Zhou, X. K., Kopelovich, L., Yantiss, R. K., Karoly, E. D., Subbaramaiah, K., & Dannenberg, A. J. (2012) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-12-0160 · Cited by 53
“Samples were processed as described previously (22, 23).”
Self-citationDiffusely infiltrating astrocytomas: pathology, molecular mechanisms and markers
Ichimura, K., Narita, Y., & Hawkins, C. E. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1439-7 · Cited by 56
“The mutated IDH requires aKG to produce D-2HG, which could originate from the conversion of glutamine via glutamate [112].”
Björkblom, B., Wibom, C., Jonsson, P., Mörén, L., Andersson, U., Johannesen, T. B., Langseth, H., Antti, H., & Melin, B. S. (2016) · Oncotarget · doi:10.18632/oncotarget.9242 · Cited by 53
“Nevertheless, brain tumors containing mutated isocitrate dehydrogenase give rise to specific metabolic signatures[10].”
BackgroundDulin, J. N., Karoly, E. D., Wang, Y., Strobel, H. W., & Grill, R. J. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.6128-11.2013 · Cited by 52
“Metabolomic profiling analysis was performed as previously described (Reitman et al., 2011).”
MethodSelf-citationCic Loss Promotes Gliomagenesis via Aberrant Neural Stem Cell Proliferation and Differentiation
Yang, R. R., Chen, L. H., Hansen, L. J., Carpenter, A. B., Moure, C. J., Liu, H., Pirozzi, C. J., Diplas, B. H., Waitkus, M. S., Greer, P. K., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-1018 · Cited by 50
Self-citationKaragiannakos, A., Adamaki, M., Tsintarakis, A., Vojtěšek, B., Fåhræus, R., Zoumpourlis, V. C., & Karakostis, K. (2022) · Cancers · doi:10.3390/cancers14030664 · Cited by 59
Glutamate as chemotactic fuel for diffuse glioma cells: Are they glutamate suckers?
van Lith, S. A. M., Navis, A. C., Verrijp, K. N., Niclou, S. P., Bjerkvig, R., Wesseling, P., Tops, B. B. J., Molenaar, R. J., Noorden, C. J. F. V., & Leenders, W. P. J. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.04.004 · Cited by 51
Denis, M. G. (2012) · International Journal of Oncology · doi:10.3892/ijo.2012.1404 · Cited by 50
“IDH1 mutations have also gained the function of catalyzing the reduction of α-ketoglutarate to 2-hydroxyglutarate (9-11).”
BackgroundVissers, L. E. L. M., Fano, V., Martinelli, D., Campos‐Xavier, B., Barbuti, D., Cho, T., Dursun, A., Kim, O. H., Lee, S. H., Timpani, G., et al. (2011) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.34325 · Cited by 49
“NAAG is a marker for neuronal cell differentiation and myelination, and its depletion in glial cells—in dependenceof thedegree of somaticmosaicismaffecting the central nervous system—might explain the cerebral atrophy seen in some MG-HGApatients.”
BackgroundSingh, B., Modica-Napolitano, J. S., & Singh, K. K. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.05.004 · Cited by 49
“High CO2 levels have been shown to be associated with decreased O2 consumption and ATP production, impaired cell proliferation, and mitochondrial dysfunction [99, 100].”
BackgroundRuyter, B., Sissener, N. H., Østbye, T.-K. K., Simon, C. J., Krasnov, A., Bou, M., Sanden, M., Nichols, P. D., Lutfi, E., & Berge, G. M. (2019) · British Journal Of Nutrition · doi:10.1017/s0007114519002356 · Cited by 47
“The metabolomics work was performed by Metabolon as previously described(30,31) with liver samples sampled from nine fish from each of the four diet groups.”
MethodLivshits, G., MacGregor, A. J., Gieger, C., Malkin, I., Moayyeri, A., Grallert, H., Emeny, R. T., Spector, T. D., Kastenmüller, G., & Williams, F. M. K. (2015) · Pain · doi:10.1097/j.pain.0000000000000200 · Cited by 45
“Nontargeted ultrahigh-performance liquid chromatography and mass spectrometry was performed on fasting plasma samples of TwinsUK participants (n 5 5003) and fasting serum samples of KORA S4 participants (n 5 1614) using the Metabolon’s platform.(24,29) The metabolomic data set contained amino acids, peptides, acylcarn…”
MethodWaitkus, M. S., Pirozzi, C. J., Moure, C. J., Diplas, B. H., Hansen, L. J., Carpenter, A. B., Yang, R. R., Wang, Z., Ingram, B. O., Karoly, E. D., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-1352 · Cited by 48
Self-citationResearch into cancer metabolomics: Towards a clinical metamorphosis
Olivares, O., Däbritz, J. H. M., King, A., Gottlieb, E., & Halsey, C. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.09.008 · Cited by 45
“inhibition exhibited selective toxicity in these gliomas [121, 122].”
BackgroundIDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy
Neal, A. J., Kwan, P., O'Brien, T. J., Buckland, M. E., Gonzales, M. F., & Morokoff, A. P. (2017) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2017.10.027 · Cited by 46
Viswanath, P., Radoul, M., Izquierdo-García, J. L., Luchman, H. A., Cairncross, J. G., Pieper, R. O., Phillips, J. J., & Ronen, S. M. (2018) · Cancer & Metabolism · doi:10.1186/s40170-018-0178-3 · Cited by 48
“who also showed reduced PC levels in IDHmut glioma cells relative to IDHwt [12].”
ResultMalzkorn, B., Wolter, M., Riemenschneider, M. J., & Reifenberger, G. (2011) · Brain Pathology · doi:10.1111/j.1750-3639.2011.00536.x · Cited by 44
“Profiling of more than 200 metabolites revealed altered levels of amino acids, glutathione metabolites, choline derivatives and tricarboxylic acid cycle intermediates in cells expressing mutant IDH1 (112), which demonstrates an extensive impact of IDH1 mutations on the cellular metabolome.”
BackgroundGenomics and metabolomics of muscular mass in a community-based sample of UK females
Korostishevsky, M., Steves, C. J., Malkin, I., Spector, T. D., Williams, F. M. K., & Livshits, G. (2015) · European Journal of Human Genetics · doi:10.1038/ejhg.2015.85 · Cited by 45
Linninger, A. A., Hartung, G. A., Liu, B. P., Mirkov, S., Tangen, K. M., Lukas, R. V., Unruh, D. J., James, C. D., Sarkaria, J. N., & Horbinski, C. (2018) · Neuro-Oncology · doi:10.1093/neuonc/noy051 · Cited by 47
A New Specific Succinate-Glutamate Metabolomic Hallmark in Sdhx-Related Paragangliomas
Impériale, A., Moussallieh, F., Sebag, F. A., Brunaud, L., Barlier, A., Elbayed, K., Bachellier, P., Goichot, B., Pacák, K., Namer, I. J., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080539 · Cited by 43
“Interestingly, IDH1/2 mutant cells are also characterized by lower levels of glutamate with respect to their wild type counterparts [27].”
BackgroundNew Directions in the Treatment of Glioblastoma
Reitman, Z. J., Winkler, F., & Elia, A. E. H. (2018) · Seminars in Neurology · doi:10.1055/s-0038-1623534 · Cited by 45
Self-citation
Metadata
- Authors
- Reitman, Z. J., Jin, G., Karoly, E. D., Spasojevic, I., Yang, J., Kinzler, K. W., He, Y., Bigner, D. D., Vogelstein, B., & Yan, H.
- Affiliations
- Duke University (US)
- Metabolon (United States) (US)
- Duke Comprehensive Cancer Center,
- The Ludwig Center and
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-02-02
- Volume
- 108
- Issue
- 8
- Pages
- 3270-3275
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3044380
- OpenAlex
- W2171026968
- Cited by
- 449
- References
- 31
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 12 · 2023: 24 · 2022: 20 · 2021: 21 · 2020: 23 · 2019: 25 · 2018: 38 · 2017: 34 · 2016: 29 · 2015: 38 · 2014: 45 · 2013: 42 · 2012: 48
- FWCI
- 24.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- American Association for Cancer Research
- Pediatric Brain Tumor Foundation
- Virginia and D.K. Ludwig Fund for Cancer Research
- National Institutes of Health
- National Cancer Institute (CA43460, 5P30-CA-014236-36, R37CA043460, R01CA140316, P30CA014236)
- 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 › Metabolomics and Mass Spectrometry Studies
- Keywords
- isocitrate dehydrogenase, IDH1 mutation, IDH2 mutation, 2-hydroxyglutarate, glioma, oligodendroglioma, N-acetylaspartylglutamate, glutathione metabolism, choline derivatives, TCA cycle intermediates, amino acids, cancer metabolism
- MeSH terms
- Dipeptides, Glioma, Glutarates, Humans, Isocitrate Dehydrogenase, Mutation, Oligodendroglioma, Cell Line, Tumor, Metabolome
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