Skip to content
2000
Volume 25, Issue 9
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Mutations in an essential metabolic enzyme, isocitrate dehydrogenase (IDH), were found in many cancers. The impact of IDH1 and IDH2 proteoforms mutations can vary and depend on the cancer type and other genetic alterations. The wild-type IDH1/2 consists of two identical subunits, but the mutant enzyme is a heterodimer of mutant and wild-type subunits, while the mutant homodimer loses its catalytic activity. Thus, the balance of expression of wild-type and mutant proteoforms directly affects enzyme neomorphic activity, cell metabolic portrait, and, therefore, cell survival and proliferation rates. Here, we generalize the influence of the presence of IDH mutations and the expression of mutant and wild-type proteoforms for various nosologies to demonstrate the deficiency in knowledge about the mutual distribution of the proteoforms in cancer cells. The review is supplemented with a brief description of IDH mutations' role in cell metabolic reprogramming and a summary of methods for IDH mutation detection. Eventually, we highlight the necessity of assessing the expression of wild-type and mutated IDH quantitatively, which can help create and deliver personalized approaches for tumor therapy.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ccdt/10.2174/0115680096317314240723054739
2024-08-28
2025-10-26

  • From This Site

    /content/journals/ccdt/10.2174/0115680096317314240723054739
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Al-KhallafH. Isocitrate dehydrogenases in physiology and cancer: Biochemical and molecular insight.Cell Biosci.2017713710.1186/s13578‑017‑0165‑3 28785398
     [Google Scholar]
  2. YangH. YeD. GuanK.L. XiongY. IDH1 and IDH2 mutations in tumorigenesis: Mechanistic insights and clinical perspectives.Clin. Cancer Res.201218205562557110.1158/1078‑0432.CCR‑12‑1773 23071358
     [Google Scholar]
  3. DangL. YenK. AttarE.C. IDH mutations in cancer and progress toward development of targeted therapeutics.Ann. Oncol.201627459960810.1093/annonc/mdw013 27005468
     [Google Scholar]
  4. LeightonF. PooleB. LazarowP.B. De DuveC. The synthesis and turnover of rat liver peroxisomes. I. Fractionation of peroxisome proteins.J. Cell Biol.196941252153510.1083/jcb.41.2.521 4389026
     [Google Scholar]
  5. RöhrigF. SchulzeA. The multifaceted roles of fatty acid synthesis in cancer.Nat. Rev. Cancer2016161173274910.1038/nrc.2016.89 27658529
     [Google Scholar]
  6. PirozziC.J. YanH. The implications of IDH mutations for cancer development and therapy.Nat. Rev. Clin. Oncol.2021181064566110.1038/s41571‑021‑00521‑0 34131315
     [Google Scholar]
  7. HanS. LiuY. CaiS.J. QianM. DingJ. LarionM. GilbertM.R. YangC. IDH mutation in glioma: Molecular mechanisms and potential therapeutic targets.Br. J. Cancer2020122111580158910.1038/s41416‑020‑0814‑x 32291392
     [Google Scholar]
  8. NovèreN.L. HuckaM. MiH. MoodieS. SchreiberF. SorokinA. DemirE. WegnerK. AladjemM.I. WimalaratneS.M. BergmanF.T. GaugesR. GhazalP. KawajiH. LiL. MatsuokaY. VillégerA. BoydS.E. CalzoneL. CourtotM. DogrusozU. FreemanT.C. FunahashiA. GhoshS. JourakuA. KimS. KolpakovF. LunaA. SahleS. SchmidtE. WattersonS. WuG. GoryaninI. KellD.B. SanderC. SauroH. SnoepJ.L. KohnK. KitanoH. The systems biology graphical notation.Nat. Biotechnol.200927873574110.1038/nbt.1558 19668183
     [Google Scholar]
  9. RougnyA. TouréV. MoodieS. BalaurI. CzaudernaT. BorlinghausH. DogrusozU. MazeinA. DrägerA. BlinovM.L. VillégerA. HawR. DemirE. MiH. SorokinA. SchreiberF. LunaA. Systems biology graphical notation: Process description language level 1 Version 2.0.J. Integr. Bioinform.20191622019002210.1515/jib‑2019‑0022 31199769
     [Google Scholar]
  10. DuX. HuH. The roles of 2-hydroxyglutarate.Front. Cell Dev. Biol.2021965131710.3389/fcell.2021.651317 33842477
     [Google Scholar]
  11. PuschS. KrausertS. FischerV. BalssJ. OttM. SchrimpfD. CapperD. SahmF. EiselJ. BeckA.C. JugoldM. EichwaldV. KaulfussS. PankninO. RehwinkelH. ZimmermannK. HilligR.C. GuentherJ. ToschiL. NeuhausR. HaegebartA. Hess-StumppH. BauserM. WickW. UnterbergA. Herold-MendeC. PlattenM. von DeimlingA. Pan-mutant IDH1 inhibitor BAY 1436032 for effective treatment of IDH1 mutant astrocytoma in vivo.Acta Neuropathol.2017133462964410.1007/s00401‑017‑1677‑y 28124097
     [Google Scholar]
  12. ShiD.D. AnandS. AbdullahK.G. McBrayerS.K. DNA damage in IDH-mutant gliomas: Mechanisms and clinical implications.J. Neurooncol.2023162351552310.1007/s11060‑022‑04172‑8 36352183
     [Google Scholar]
  13. RizzoA. BrandiG. Pitfalls, challenges, and updates in adjuvant systemic treatment for resected biliary tract cancer.Expert Rev. Gastroenterol. Hepatol.202115554755410.1080/17474124.2021.1890031 33571059
     [Google Scholar]
  14. RizzoA. RicciA.D. ToberN. NigroM.C. MoscaM. PalloniA. AbbatiF. FregaG. De LorenzoS. TavolariS. BrandiG. Second-line treatment in advanced biliary tract cancer: Today and tomorrow.Anticancer Res.20204063013303010.21873/anticanres.14282 32487595
     [Google Scholar]
  15. HuX. LiL. EidJ.E. LiuC. YuJ. YueJ. TrentJ.C. IDH1 mutation induces HIF-1α and Confers angiogenic properties in chondrosarcoma JJ012 cells.Dis. Markers2022202211110.1155/2022/7729968 35198082
     [Google Scholar]
  16. KickingerederP. SahmF. RadbruchA. WickW. HeilandS. DeimlingA. BendszusM. WiestlerB. IDH mutation status is associated with a distinct hypoxia/angiogenesis transcriptome signature which is non-invasively predictable with rCBV imaging in human glioma.Sci. Rep.2015511623810.1038/srep16238 26538165
     [Google Scholar]
  17. YeD. XiongY. GuanK.L. The mechanisms of IDH mutations in tumorigenesis.Cell Res.20122271102110410.1038/cr.2012.51 22453240
     [Google Scholar]
  18. NikitinP.V. PotapovA.A. RyzhovaM.V. ShurkhayV.A. KulikovE.E. ZhvanskiyE.S. PopovI.A. NikolaevE.N. The role of lipid metabolism disorders, atypical isoforms of protein kinase C, and mutational status of cytosolic and mitochondrial forms of isocitrate dehydrogenase in carcinogenesis of glial tumors.Vopr. Neirokhir.201882311212010.17116/neiro2018823112 29927433
     [Google Scholar]
  19. MiH. SchreiberF. MoodieS. CzaudernaT. DemirE. HawR. LunaA. Le NovèreN. SorokinA. VillégerA. Systems biology graphical notation: Activity flow language Level 1 Version 1.2.J. Integr. Bioinform.201512234038110.1515/jib‑2015‑265 26528563
     [Google Scholar]
  20. XuX. ZhaoJ. XuZ. PengB. HuangQ. ArnoldE. DingJ. Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity.J. Biol. Chem.200427932339463395710.1074/jbc.M404298200 15173171
     [Google Scholar]
  21. SunP. LiuY. MaT. DingJ. Structure and Allosteric Regulation of Human IDH3 Holoenzyme.bioRxiv202010.1101/2020.06.25.170399
     [Google Scholar]
  22. YanH. ParsonsD.W. JinG. McLendonR. RasheedB.A. YuanW. KosI. Batinic-HaberleI. JonesS. RigginsG.J. FriedmanH. FriedmanA. ReardonD. HerndonJ. KinzlerK.W. VelculescuV.E. VogelsteinB. BignerD.D. IDH1 and IDH2 mutations in gliomas.N. Engl. J. Med.2009360876577310.1056/NEJMoa0808710 19228619
     [Google Scholar]
  23. ThomasD. WuM. NakauchiY. ZhengM. Thompson-PeachC.A.L. LimK. LandbergN. KöhnkeT. RobinsonN. KaurS. KutynaM. StaffordM. HiwaseD. ReinischA. PeltzG. MajetiR. Dysregulated lipid synthesis by oncogenic IDH1 mutation is a targetable synthetic lethal vulnerability.Cancer Discov.202313249651510.1158/2159‑8290.CD‑21‑0218 36355448
     [Google Scholar]
  24. MillerJ.J. Gonzalez CastroL.N. McBrayerS. WellerM. CloughesyT. PortnowJ. AndronesiO. Barnholtz-SloanJ.S. BaumertB.G. BergerM.S. BiW.L. BindraR. CahillD.P. ChangS.M. CostelloJ.F. HorbinskiC. HuangR.Y. JenkinsR.B. LigonK.L. MellinghoffI.K. NaborsL.B. PlattenM. ReardonD.A. ShiD.D. SchiffD. WickW. YanH. von DeimlingA. van den BentM. KaelinW.G. WenP.Y. Isocitrate dehydrogenase (IDH) mutant gliomas: A Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions.Neuro-oncol.202325142510.1093/neuonc/noac207 36239925
     [Google Scholar]
  25. BadurM.G. MuthusamyT. ParkerS.J. MaS. McBrayerS.K. CordesT. MaganaJ.H. GuanK.L. MetalloC.M. Oncogenic R132 IDH1 Mutations Limit NADPH for De Novo Lipogenesis through (D)2-Hydroxyglutarate Production in Fibrosarcoma Cells.Cell Rep.201825410181026.e410.1016/j.celrep.2018.09.074 30355481
     [Google Scholar]
  26. TurkalpZ. KaramchandaniJ. DasS. IDH mutation in glioma: New insights and promises for the future.JAMA Neurol.201471101319132510.1001/jamaneurol.2014.1205 25155243
     [Google Scholar]
  27. Ruiz-RodadoV. LitaA. DowdyT. CelikuO. SaldanaA.C. WangH. YangC.Z. ChariR. LiA. ZhangW. SongH. ZhangM. AhnS. DavisD. ChenX. ZhuangZ. Herold-MendeC. WaltersK.J. GilbertM.R. LarionM. Metabolic plasticity of IDH1-mutant glioma cell lines is responsible for low sensitivity to glutaminase inhibition.Cancer Metab.2020812310.1186/s40170‑020‑00229‑2 33101674
     [Google Scholar]
  28. GuoJ. ZhangR. YangZ. DuanZ. YinD. ZhouY. Biological roles and therapeutic applications of IDH2 mutations in human cancer.Front. Oncol.20211164485710.3389/fonc.2021.644857 33981605
     [Google Scholar]
  29. KanwalM. SmahelM. OlsenM. SmahelovaJ. TachezyR. Aspartate β-hydroxylase as a target for cancer therapy.J. Exp. Clin. Cancer Res.202039116310.1186/s13046‑020‑01669‑w 32811566
     [Google Scholar]
  30. StuaniL. SabatierM. SalandE. CognetG. PoupinN. BoscC. CastelliF.A. GalesL. TurtoiE. MontersinoC. FargeT. BoetE. BroinN. LarrueC. BaranN. CisséM.Y. ContiM. LoricS. KaomaT. HucteauA. ZavoritiA. SahalA. MouchelP.L. GotanègreM. CassanC. FernandoL. WangF. HosseiniM. Chu-VanE. Le CamL. CarrollM. SelakM.A. VeyN. CastellanoR. FenailleF. TurtoiA. CazalsG. BoriesP. GibonY. NicolayB. RonseauxS. MarszalekJ.R. TakahashiK. DiNardoC.D. KonoplevaM. PancaldiV. ColletteY. BellvertF. JourdanF. LinaresL.K. RécherC. PortaisJ.C. SarryJ.E. Mitochondrial metabolism supports resistance to IDH mutant inhibitors in acute myeloid leukemia.J. Exp. Med.20212185e2020092410.1084/jem.20200924 33760042
     [Google Scholar]
  31. KaminskaB. CzapskiB. GuzikR. KrólS.K. GielniewskiB. Consequences of IDH1/2 mutations in gliomas and an assessment of inhibitors targeting mutated IDH proteins.Molecules201924596810.3390/molecules24050968 30857299
     [Google Scholar]
  32. PekovS.I. SorokinA.A. KuzinA.A. BocharovK.V. BormotovD.S. ShivalinA.S. ShurkhayV.A. PotapovA.A. NikolaevE.N. PopovI.A. Analysis of phosphatidylcholines alterations in human glioblastomas ex vivo.Biochem. Suppl. Ser. B: Biomed. Chem.202115324124710.1134/S1990750821030070
     [Google Scholar]
  33. McKelveyK.J. WilsonE.B. ShortS. MelcherA.A. BiggsM. DiakosC.I. HowellV.M. Glycolysis and fatty acid oxidation inhibition improves survival in glioblastoma.Front. Oncol.20211163321010.3389/fonc.2021.633210 33854970
     [Google Scholar]
  34. LouisD.N. PerryA. WesselingP. BratD.J. CreeI.A. Figarella-BrangerD. HawkinsC. NgH.K. PfisterS.M. ReifenbergerG. SoffiettiR. von DeimlingA. EllisonD.W. The 2021 WHO classification of tumors of the central nervous system: A summary.Neuro-oncol.20212381231125110.1093/neuonc/noab106 34185076
     [Google Scholar]
  35. ŚledzińskaP. BebynM.G. FurtakJ. KowalewskiJ. LewandowskaM.A. Prognostic and predictive biomarkers in gliomas.Int. J. Mol. Sci.202122191037310.3390/ijms221910373 34638714
     [Google Scholar]
  36. SorokinA. ShurkhayV. PekovS. ZhvanskyE. IvanovD. KulikovE.E. PopovI. PotapovA. NikolaevE. Untangling the metabolic reprogramming in brain cancer: Discovering key molecular players using mass spectrometry.Curr. Top. Med. Chem.201919171521153410.2174/1568026619666190729154543 31362676
     [Google Scholar]
  37. DonoA. BallesterL.Y. PrimdahlD. EsquenaziY. BhatiaA. IDH-mutant low-grade glioma: Advances in molecular diagnosis, management, and future directions.Curr. Oncol. Rep.20212322010.1007/s11912‑020‑01006‑6 33492489
     [Google Scholar]
  38. HartmannC. MeyerJ. BalssJ. CapperD. MuellerW. ChristiansA. FelsbergJ. WolterM. MawrinC. WickW. WellerM. Herold-MendeC. UnterbergA. JeukenJ.W.M. WesselingP. ReifenbergerG. von DeimlingA. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: A study of 1,010 diffuse gliomas.Acta Neuropathol.2009118446947410.1007/s00401‑009‑0561‑9 19554337
     [Google Scholar]
  39. MuruganA.K. AlzahraniA.S. Isocitrate dehydrogenase IDH1 and IDH2 mutations in human cancer: Prognostic implications for gliomas.Br. J. Biomed. Sci.2022791020810.3389/bjbs.2021.10208 35996504
     [Google Scholar]
  40. HaiderA.S. EneC.I. PalmiscianoP. HaiderM. RaoG. BallesterL.Y. FullerG.N. Concurrent IDH1 and IDH2 mutations in glioblastoma: A case report.Front. Oncol.202313107179210.3389/fonc.2023.1071792 37077830
     [Google Scholar]
  41. MorganL.R. SaricaF.B. Brain and Spinal Tumors - Primary and Secondary.LondonIntechOpen202010.5772/intechopen.77682
     [Google Scholar]
  42. KandalgaonkarP. SahuA. SajuA.C. JoshiA. MahajanA. ThakurM. SahayA. EpariS. SinhaS. DasguptaA. ChatterjeeA. ShettyP. MoiyadiA. AgarwalJ. GuptaT. GodaJ.S. Predicting IDH subtype of grade 4 astrocytoma and glioblastoma from tumor radiomic patterns extracted from multiparametric magnetic resonance images using a machine learning approach.Front. Oncol.20221287937610.3389/fonc.2022.879376 36276136
     [Google Scholar]
  43. Ramos-FresnedoA. PullenM.W. Perez-VegaC. DomingoR.A. AkinduroO.O. AlmeidaJ.P. Suarez-MeadeP. Marenco-HillembrandL. JentoftM.E. BendokB.R. TrifilettiD.M. ChaichanaK.L. PorterA.B. Quiñones-HinojosaA. BurnsT.C. KizilbashS.H. MiddlebrooksE.H. ShermanW.J. The survival outcomes of molecular glioblastoma IDH-wildtype: A multicenter study.J. Neurooncol.2022157117718510.1007/s11060‑022‑03960‑6 35175545
     [Google Scholar]
  44. BurgenskeD.M. YangJ. DeckerP.A. KollmeyerT.M. KoselM.L. MladekA.C. CaronA.A. VaubelR.A. GuptaS.K. KitangeG.J. SicotteH. YoulandR.S. RemondeD. VossJ.S. FritcherE.G.B. KolskyK.L. IdaC.M. MeyerF.B. LachanceD.H. ParneyI.J. KippB.R. GianniniC. SulmanE.P. JenkinsR.B. Eckel-PassowJ.E. SarkariaJ.N. Molecular profiling of long-term IDH-wildtype glioblastoma survivors.Neuro-oncol.201921111458146910.1093/neuonc/noz129 31346613
     [Google Scholar]
  45. GalbraithK. KumarA. AbdullahK.G. WalkerJ.M. AdamsS.H. PriorT. DimentbergR. HendersonF.C. MirchiaK. SatheA.A. ViapianoM.S. ChinL.S. CoronaR.J. HatanpaaK.J. SnuderlM. XingC. BremS. RichardsonT.E. Molecular correlates of long survival in IDH-wildtype glioblastoma cohorts.J. Neuropathol. Exp. Neurol.202079884385410.1093/jnen/nlaa059 32647886
     [Google Scholar]
  46. BergaggioE. PivaR. Wild-type IDH enzymes as actionable targets for cancer therapy.Cancers201911456310.3390/cancers11040563 31010244
     [Google Scholar]
  47. TanakaH. SasayamaT. TanakaK. NakamizoS. NishiharaM. MizukawaK. KohtaM. KoyamaJ. MiyakeS. TaniguchiM. HosodaK. KohmuraE. MicroRNA-183 upregulates HIF-1α by targeting isocitrate dehydrogenase 2 (IDH2) in glioma cells.J. Neurooncol.2013111327328310.1007/s11060‑012‑1027‑9 23263745
     [Google Scholar]
  48. BrindleyP.J. BachiniM. IlyasS.I. KhanS.A. LoukasA. SiricaA.E. TehB.T. WongkhamS. GoresG.J. Cholangiocarcinoma.Nat. Rev. Dis. Primers2021716510.1038/s41572‑021‑00300‑2 34504109
     [Google Scholar]
  49. MaB. MengH. TianY. WangY. SongT. ZhangT. WuQ. CuiY. LiH. ZhangW. LiQ. Distinct clinical and prognostic implication of IDH1/2 mutation and other most frequent mutations in large duct and small duct subtypes of intrahepatic cholangiocarcinoma.BMC Cancer202020131810.1186/s12885‑020‑06804‑6 32293336
     [Google Scholar]
  50. AminM.B. EdgeS.B. GreeneF.L. ByrdD.R. BrooklandR.K. WashingtonM.K. GershenwaldJ.E. ComptonC.C. HessK.R. SullivanD.C. AJCC Cancer Staging Manual.ChamSpringer20171024
     [Google Scholar]
  51. FedorovaO.S. FedotovaM.M. ZvonarevaO.I. MazeinaS.V. KovshirinaY.V. SokolovaT.S. GolovachE.A. KovshirinaA.E. KonovalovaU.V. KolomeetsI.L. GutorS.S. PetrovV.A. HattendorfJ. OgorodovaL.M. OdermattP. Opisthorchis felineus infection, risks, and morbidity in rural Western Siberia, Russian Federation.PLoS Negl. Trop. Dis.2020146e000842110.1371/journal.pntd.0008421 32598389
     [Google Scholar]
  52. OliveiraI.S. KilcoyneA. EverettJ.M. Mino-KenudsonM. HarisinghaniM.G. GanesanK. Cholangiocarcinoma: Classification, diagnosis, staging, imaging features, and management.Abdom. Radiol.20174261637164910.1007/s00261‑017‑1094‑7 28271275
     [Google Scholar]
  53. Bruce-BrandC. GovenderD. Gene of the month: IDH1.J. Clin. Pathol.2020731061161510.1136/jclinpath‑2020‑206813 32727816
     [Google Scholar]
  54. KimN.I. NohM.G. KimJ.H. WonE.J. LeeY.J. HurY. MoonK.S. LeeK.H. LeeJ.H. Frequency and prognostic value of IDH mutations in korean patients with cholangiocarcinoma.Front. Oncol.202010151410.3389/fonc.2020.01514 33014795
     [Google Scholar]
  55. BrandiG. DeianaC. GalvaniL. PalloniA. RicciA.D. RizzoA. TavolariS. Are FGFR and IDH1-2 alterations a positive prognostic factor in intrahepatic cholangiocarcinoma? An unresolved issue.Front. Oncol.202313113751010.3389/fonc.2023.1137510 37168376
     [Google Scholar]
  56. BoscoeA.N. RollandC. KelleyR.K. Frequency and prognostic significance of isocitrate dehydrogenase 1 mutations in cholangiocarcinoma: A systematic literature review.J. Gastrointest. Oncol.201910475176510.21037/jgo.2019.03.10 31392056
     [Google Scholar]
  57. Abou-AlfaG.K. Macarulla MercadeT. JavleM. KelleyR.K. LubnerS. AdevaJ. ClearyJ.M. CatenacciD.V. BoradM.J. BridgewaterJ.A. HarrisW.P. MurphyA.G. OhD.Y. WhisenantJ. WuB. JiangL. GliserC. PandyaS.S. ValleJ.W. ZhuA.X. ClarIDHy: A global, phase III, randomized, double-blind study of ivosidenib (IVO) vs placebo in patients with advanced cholangiocarcinoma (CC) with an isocitrate dehydrogenase 1 (IDH1) mutation.Ann. Oncol.201930v872v87310.1093/annonc/mdz394.027
     [Google Scholar]
  58. ZhuA.X. MacarullaT. JavleM.M. KelleyR.K. LubnerS.J. AdevaJ. ClearyJ.M. CatenacciD.V.T. BoradM.J. BridgewaterJ.A. HarrisW.P. MurphyA.G. OhD.Y. WhisenantJ.R. LoweryM.A. GoyalL. ShroffR.T. El-KhoueiryA.B. ChamberlainC.X. Aguado-FraileE. ChoeS. WuB. LiuH. GliserC. PandyaS.S. ValleJ.W. Abou-AlfaG.K. Final overall survival efficacy results of ivosidenib for patients with advanced cholangiocarcinoma with IDH1 mutation.JAMA Oncol.20217111669167710.1001/jamaoncol.2021.3836 34554208
     [Google Scholar]
  59. American Association for Cancer ResearchIvosidenib boosts OS in cholangiocarcinoma.Cancer Discov.202111122953295410.1158/2159‑8290.CD‑NB2021‑0389 34635569
     [Google Scholar]
  60. WuM.J. ShiL. MerrittJ. ZhuA.X. BardeesyN. Biology of IDH mutant cholangiocarcinoma.Hepatology20227551322133710.1002/hep.32424 35226770
     [Google Scholar]
  61. SalatiM. CaputoF. BaldessariC. GalassiB. GrossiF. DominiciM. GhidiniM. IDH signalling pathway in cholangiocarcinoma: From biological rationale to therapeutic targeting.Cancers20201211331010.3390/cancers12113310 33182517
     [Google Scholar]
  62. RichardsonL.G. MillerJ.J. KitagawaY. WakimotoH. ChoiB.D. CurryW.T. Implications of IDH mutations on immunotherapeutic strategies for malignant glioma.Neurosurg. Focus2022522E610.3171/2021.11.FOCUS21604 35104795
     [Google Scholar]
  63. ArrangoizR. CorderaF. CabaD. MorenoE. Luque-de-LeonE. MuñozM. Thyroid Cancer.Int J Otolaryngol Head Neck Surg20198621727010.4236/ijohns.2019.86024
     [Google Scholar]
  64. GimmO. Thyroid cancer.Cancer Lett.2001163214315610.1016/S0304‑3835(00)00697‑2 11165748
     [Google Scholar]
  65. MuruganA. QasemE. Al-HindiH. AlzahraniA. Analysis of ALK, IDH1, IDH2 and MMP8 somatic mutations in differentiated thyroid cancers.Mol. Clin. Oncol.202115421010.3892/mco.2021.2373 34462665
     [Google Scholar]
  66. MuruganA.K. BojdaniE. XingM. Identification and functional characterization of isocitrate dehydrogenase 1 (IDH1) mutations in thyroid cancer.Biochem. Biophys. Res. Commun.2010393355555910.1016/j.bbrc.2010.02.095 20171178
     [Google Scholar]
  67. ZhangJ. HuL. WangH. ZhiJ. HouX. WuY. ZhengX. GaoM. Functional analysis and clinical significance of the isocitrate dehydrogenase 2 gene in papillary thyroid carcinoma.Cancer Manag. Res.2019113765377710.2147/CMAR.S194920 31118795
     [Google Scholar]
  68. KhatamiF. PayabM. SarvariM. GilanyK. LarijaniB. ArjmandB. TavangarS.M. Oncometabolites as biomarkers in thyroid cancer: A systematic review.Cancer Manag. Res.2019111829184110.2147/CMAR.S188661 30881111
     [Google Scholar]
  69. El AchiH. Kanagal-ShamannaR. Biomarkers in acute myeloid leukemia: Leveraging next generation sequencing data for optimal therapeutic strategies.Front. Oncol.20211174825010.3389/fonc.2021.748250 34660311
     [Google Scholar]
  70. CerchioneC. RomanoA. DaverN. DiNardoC. JabbourE.J. KonoplevaM. Ravandi-KashaniF. KadiaT. MartelliM.P. IsidoriA. MartinelliG. KantarjianH. IDH1/IDH2 inhibition in acute myeloid leukemia.Front. Oncol.20211163938710.3389/fonc.2021.639387 33898313
     [Google Scholar]
  71. PaschkaP. SchlenkR.F. GaidzikV.I. HabdankM. KrönkeJ. BullingerL. SpäthD. KayserS. ZucknickM. GötzeK. HorstH.A. GermingU. DöhnerH. DöhnerK. IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication.J. Clin. Oncol.201028223636364310.1200/JCO.2010.28.3762 20567020
     [Google Scholar]
  72. KunadtD. StasikS. MetzelerK.H. RölligC. SchliemannC. GreifP.A. SpiekermannK. Rothenberg-ThurleyM. KrugU. BraessJ. KrämerA. HochhausA. SchollS. HilgendorfI. BrümmendorfT.H. JostE. SteffenB. BugG. EinseleH. GörlichD. SauerlandC. Schäfer-EckartK. KrauseS.W. HänelM. HanounM. KaufmannM. WörmannB. KramerM. SockelK. Egger-HeidrichK. HeroldT. EhningerG. BurchertA. PlatzbeckerU. BerdelW.E. Müller-TidowC. HiddemannW. ServeH. StelljesM. BaldusC.D. NeubauerA. ScheteligJ. ThiedeC. BornhäuserM. MiddekeJ.M. StölzelF. Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation.J. Hematol. Oncol.202215112610.1186/s13045‑022‑01339‑8 36064577
     [Google Scholar]
  73. TholF. DammF. WagnerK. GöhringG. SchlegelbergerB. HoelzerD. LübbertM. HeitW. KanzL. SchlimokG. RaghavacharA. FiedlerW. KirchnerH. HeilG. HeuserM. KrauterJ. GanserA. Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia.Blood2010116461461610.1182/blood‑2010‑03‑272146 20421455
     [Google Scholar]
  74. MaQ.L. WangJ.H. WangY.G. HuC. MuQ.T. YuM.X. WangL. WangD.M. YangM. YinX.F. ChenF.F. LuS.S. ChenJ. ZhuZ.J. ChenS.J. JinJ. High IDH1 expression is associated with a poor prognosis in cytogenetically normal acute myeloid leukemia.Int. J. Cancer201513751058106510.1002/ijc.29395 25523507
     [Google Scholar]
  75. HuangJ. TsengL.H. PariniV. LokhandwalaP.M. PallavajjalaA. RodriguezE. XianR. ChenL. GockeC.D. EshlemanJ.R. LinM.T. IDH1 and IDH2 Mutations in Colorectal Cancers.Am. J. Clin. Pathol.2021156577778610.1093/ajcp/aqab023 33929516
     [Google Scholar]
  76. ClarkO. YenK. MellinghoffI.K. Molecular pathways: Isocitrate dehydrogenase mutations in cancer.Clin. Cancer Res.20162281837184210.1158/1078‑0432.CCR‑13‑1333 26819452
     [Google Scholar]
  77. LexJ.R. EvansS. StevensonJ.D. ParryM. JeysL.M. GrimerR.J. Dedifferentiated chondrosarcoma of the pelvis: Clinical outcomes and current treatment.Clin. Sarcoma Res.2018812310.1186/s13569‑018‑0110‑1 30559960
     [Google Scholar]
  78. KimJ.H. LeeS.K. Classification of chondrosarcoma: From characteristic to challenging imaging findings.Cancers2023156170310.3390/cancers15061703 36980590
     [Google Scholar]
  79. VennekerS. KruisselbrinkA.B. BaranskiZ. PalubeckaiteI. Briaire-de BruijnI.H. OostingJ. FrenchP.J. DanenE.H.J. BovéeJ.V.M.G. Beyond the Influence of IDH mutations: Exploring epigenetic vulnerabilities in chondrosarcoma.Cancers20201212358910.3390/cancers12123589 33266275
     [Google Scholar]
  80. CojocaruE. WildingC. EngelmanB. HuangP. JonesR.L. Is the IDH mutation a good target for chondrosarcoma treatment?Curr. Mol. Biol. Rep.2020611910.1007/s40610‑020‑00126‑z
     [Google Scholar]
  81. AmaryM.F. BacsiK. MaggianiF. DamatoS. HalaiD. BerishaF. PollockR. O’DonnellP. GrigoriadisA. DissT. EskandarpourM. PresneauN. HogendoornP.C.W. FutrealA. TiraboscoR. FlanaganA.M. IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours.J. Pathol.2011224333434310.1002/path.2913 21598255
     [Google Scholar]
  82. CoteG.M. HeJ. ChoyE. Next-generation sequencing for patients with sarcoma: A single center experience.Oncologist201823223424210.1634/theoncologist.2017‑0290 28860410
     [Google Scholar]
  83. WeinschenkR.C. WangW.L. LewisV.O. Chondrosarcoma.J. Am. Acad. Orthop. Surg.2021291355356210.5435/JAAOS‑D‑20‑01188 33595238
     [Google Scholar]
  84. ClevenA.H.G. SuijkerJ. AgrogiannisG. Briaire-de BruijnI.H. FrizzellN. HoekstraA.S. Wijers-KosterP.M. Cleton-JansenA.M. BovéeJ.V.M.G. IDH1 or -2 mutations do not predict outcome and do not cause loss of 5-hydroxymethylcytosine or altered histone modifications in central chondrosarcomas.Clin. Sarcoma Res.201771810.1186/s13569‑017‑0074‑6 28484589
     [Google Scholar]
  85. PathmanapanS. IlkayevaO. MartinJ.T. LoeA.K.H. ZhangH. ZhangG.F. NewgardC.B. WunderJ.S. AlmanB.A. Mutant IDH and non-mutant chondrosarcomas display distinct cellular metabolomes.Cancer Metab.2021911310.1186/s40170‑021‑00247‑8 33762012
     [Google Scholar]
  86. HsuY.L. LinC.C. JiangJ.K. LinH.H. LanY.T. WangH.S. YangS.H. ChenW.S. LinT.C. LinJ.K. LinP.C. ChangS.C. Clinicopathological and molecular differences in colorectal cancer according to location.Int. J. Biol. Markers2019341475310.1177/1724600818807164 30854932
     [Google Scholar]
  87. ZhuangY. WangH. JiangD. LiY. FengL. TianC. PuM. WangX. ZhangJ. HuY. LiuP. Multi gene mutation signatures in colorectal cancer patients: Predict for the diagnosis, pathological classification, staging and prognosis.BMC Cancer202121138010.1186/s12885‑021‑08108‑9 33836681
     [Google Scholar]
  88. LvQ. XingS. LiZ. LiJ. GongP. XuX. ChangL. JinX. GaoF. LiW. ZhangG. YangJ. ZhangX. Altered expression levels of IDH2 are involved in the development of colon cancer.Exp. Ther. Med.20124580180610.3892/etm.2012.676 23226729
     [Google Scholar]
  89. KosekiJ. ColvinH. FukusumiT. NishidaN. KonnoM. KawamotoK. TsunekuniK. MatsuiH. DokiY. MoriM. IshiiH. Mathematical analysis predicts imbalanced IDH1/2 expression associates with 2-HG-inactivating β-oxygenation pathway in colorectal cancer.Int. J. Oncol.20154631181119110.3892/ijo.2015.2833 25586680
     [Google Scholar]
  90. OdejideO. WeigertO. LaneA.A. ToscanoD. LunningM.A. KoppN. KimS. van BodegomD. BollaS. SchatzJ.H. Teruya-FeldsteinJ. HochbergE. LouissaintA. DorfmanD. StevensonK. RodigS.J. PiccalugaP.P. JacobsenE. PileriS.A. HarrisN.L. FerreroS. InghiramiG. HorwitzS.M. WeinstockD.M. A targeted mutational landscape of angioimmunoblastic T-cell lymphoma.Blood201412391293129610.1182/blood‑2013‑10‑531509 24345752
     [Google Scholar]
  91. SimoninM. SchmidtA. BontouxC. DourtheM.É. LenglinéE. AndrieuG.P. LhermitteL. GrauxC. GrardelN. CayuelaJ.M. HuguetF. ArnouxI. DucassouS. MacintyreE. GandemerV. DombretH. PetitA. IfrahN. BaruchelA. BoisselN. AsnafiV. Oncogenetic landscape and clinical impact of IDH1 and IDH2 mutations in T-ALL.J. Hematol. Oncol.20211417410.1186/s13045‑021‑01068‑4 33941203
     [Google Scholar]
  92. CairnsR.A. IqbalJ. LemonnierF. KucukC. de LevalL. JaisJ.P. ParrensM. MartinA. XerriL. BroussetP. ChanL.C. ChanW.C. GaulardP. MakT.W. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma.Blood201211981901190310.1182/blood‑2011‑11‑391748 22215888
     [Google Scholar]
  93. LemonnierF. CairnsR.A. InoueS. LiW.Y. DupuyA. BroutinS. MartinN. FataccioliV. PelletierR. WakehamA. SnowB.E. de LevalL. PujalsA. HaiounC. PaciA. TobinE.R. NarayanaswamyR. YenK. JinS. GaulardP. MakT.W. The IDH2 R172K mutation associated with angioimmunoblastic T-cell lymphoma produces 2HG in T cells and impacts lymphoid development.Proc. Natl. Acad. Sci. USA201611352150841508910.1073/pnas.1617929114 27956631
     [Google Scholar]
  94. AlsadounN. MacGroganG. TruntzerC. Lacroix-TrikiM. BedgedjianI. KoebM.H. El AlamE. MedioniD. ParentM. WuithierP. RobertI. BoidotR. ArnouldL. Solid papillary carcinoma with reverse polarity of the breast harbors specific morphologic, immunohistochemical and molecular profile in comparison with other benign or malignant papillary lesions of the breast: A comparative study of 9 additional cases.Mod. Pathol.20183191367138010.1038/s41379‑018‑0047‑1 29785016
     [Google Scholar]
  95. ChiangS. WeigeltB. WenH.C. ParejaF. RaghavendraA. MartelottoL.G. BurkeK.A. BasiliT. LiA. GeyerF.C. PiscuoglioS. NgC.K.Y. JungbluthA.A. BalssJ. PuschS. BakerG.M. ColeK.S. von DeimlingA. BattenJ.M. MarottiJ.D. SohH.C. McCalipB.L. SerranoJ. LimR.S. SiziopikouK.P. LuS. LiuX. HammourT. BrogiE. SnuderlM. IafrateA.J. Reis-FilhoJ.S. SchnittS.J. IDH2 mutations define a unique subtype of breast cancer with altered nuclear polarity.Cancer Res.201676247118712910.1158/0008‑5472.CAN‑16‑0298 27913435
     [Google Scholar]
  96. PreusserM. CapperD. HartmannC. IDH testing in diagnostic neuropathology: Review and practical guideline article invited by the Euro-CNS research committee.Clin. Neuropathol.201130921723010.5414/NP300422 21955925
     [Google Scholar]
  97. CapperD. WeißertS. BalssJ. HabelA. MeyerJ. JägerD. AckermannU. TessmerC. KorshunovA. ZentgrafH. HartmannC. Von DeimlingA. Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors.Brain Pathol.201020124525410.1111/j.1750‑3639.2009.00352.x 19903171
     [Google Scholar]
  98. FelsbergJ. WolterM. SeulH. FriedensdorfB. GöppertM. SabelM.C. ReifenbergerG. Rapid and sensitive assessment of the IDH1 and IDH2 mutation status in cerebral gliomas based on DNA pyrosequencing.Acta Neuropathol.2010119450150710.1007/s00401‑010‑0647‑4 20131059
     [Google Scholar]
  99. MeyerJ. PuschS. BalssJ. CapperD. MuellerW. ChristiansA. HartmannC. Von DeimlingA. PCR- and restriction endonuclease-based detection of IDH1 mutations.Brain Pathol.201020229830010.1111/j.1750‑3639.2009.00327.x 19744125
     [Google Scholar]
  100. PerizzoloM. WinkfeinB. HuiS. KrulickiW. ChanJ.A. DemetrickD.J. IDH mutation detection in formalin-fixed paraffin-embedded gliomas using multiplex PCR and single-base extension.Brain Pathol.201222561962410.1111/j.1750‑3639.2012.00579.x 22360629
     [Google Scholar]
  101. HorbinskiC. KellyL. NikiforovY.E. DursoM.B. NikiforovaM.N. Detection of IDH1 and IDH2 mutations by fluorescence melting curve analysis as a diagnostic tool for brain biopsies.J. Mol. Diagn.201012448749210.2353/jmoldx.2010.090228 20431032
     [Google Scholar]
  102. BujkoM. KoberP. MatyjaE. NaumanP. Dyttus-CebulokK. CzeremszyńskaB. BonickiW. SiedleckiJ.A. Prognostic value of IDH1 mutations identified with PCR-RFLP assay in glioblastoma patients.Mol. Diagn. Ther.201014316316910.1007/BF03256369 20560678
     [Google Scholar]
  103. BoisselierB. MarieY. LabussièreM. CiccarinoP. DesestretV. WangX. CapelleL. DelattreJ.Y. SansonM. COLD PCR HRM: A highly sensitive detection method for IDH1 mutations.Hum. Mutat.201031121360136510.1002/humu.21365 20886613
     [Google Scholar]
  104. LiY. QinQ. ZhangY. CaoY. Noninvasive determination of the IDH status of gliomas using MRI and MRI-based radiomics: Impact on diagnosis and prognosis.Curr. Oncol.202229106893690710.3390/curroncol29100542 36290819
     [Google Scholar]
  105. FeracoP. BacciA. FerrazzaP. van den HauweL. PertileR. GirlandoS. BarbareschiM. GagliardoC. MorgantiA.G. PetraliaB. Magnetic resonance imaging derived biomarkers of IDH mutation status and overall survival in Grade III astrocytomas.Diagnostics202010424710.3390/diagnostics10040247 32340318
     [Google Scholar]
  106. HaapalaI. RauhameriA. RoineA. MäkeläM. KontunenA. KarjalainenM. LaaksoA. Koroknay-PálP. NordforsK. HaapasaloH. OksalaN. VehkaojaA. HaapasaloJ. Method for the intraoperative detection of IDH mutation in gliomas with differential mobility spectrometry.Curr. Oncol.20222953252325810.3390/curroncol29050265 35621655
     [Google Scholar]
  107. AkyerliC.B. YükselŞ. CanÖ. Erson-OmayE.Z. OktayY. CoşgunE. ÜlgenE. ErdemgilY. SavA. von DeimlingA. GünelM. YakıcıerM.C. PamirM.N. ÖzdumanK. Use of telomerase promoter mutations to mark specific molecular subsets with reciprocal clinical behavior in IDH mutant and IDH wild-type diffuse gliomas.J. Neurosurg.201812841102111410.3171/2016.11.JNS16973 28621624
     [Google Scholar]
  108. FujimotoK. AritaH. SatomiK. YamasakiK. MatsushitaY. NakamuraT. MiyakitaY. UmeharaT. KobayashiK. TamuraK. TanakaS. HiguchiF. OkitaY. KanemuraY. FukaiJ. SakamotoD. UdaT. MachidaR. KuchibaA. MaeharaT. NaganeM. NishikawaR. SuzukiH. ShibuyaM. KomoriT. NaritaY. IchimuraK. TERT promoter mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic glioma with molecular features of glioblastoma.Acta Neuropathol.2021142232333810.1007/s00401‑021‑02337‑9 34148105
     [Google Scholar]
  109. Noble AnbunesanS. Alfonso-GarciaA. ZhouX. BecJ. LeeH.S. JinL.W. BlochO. MarcuL. Intraoperative detection of IDH ‐mutant glioma using fluorescence lifetime imaging.J. Biophotonics2023164e20220029110.1002/jbio.202200291 36510639
     [Google Scholar]
  110. LeatherT. JenkinsonM. DasK. PoptaniH. Magnetic resonance spectroscopy for detection of 2-hydroxyglutarate as a biomarker for IDH mutation in gliomas.Metabolites2017722910.3390/metabo7020029 28629182
     [Google Scholar]
  111. DangL. WhiteD.W. GrossS. BennettB.D. BittingerM.A. DriggersE.M. FantinV.R. JangH.G. JinS. KeenanM.C. MarksK.M. PrinsR.M. WardP.S. YenK.E. LiauL.M. RabinowitzJ.D. CantleyL.C. ThompsonC.B. Vander HeidenM.G. SuS.M. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate.Nature2009462727473974410.1038/nature08617 19935646
     [Google Scholar]
  112. SuhC.H. KimH.S. ParkJ.E. JungS.C. ChoiC.G. WooD.C. LeeH.B. KimS.J. Comparative value of 2-hydroxyglutarate–to–lipid and lactate ratio versus 2-hydroxyglutarate concentration on MR spectroscopic images for predicting isocitrate dehydrogenase mutation status in gliomas.Radiol. Imaging Cancer202024e19008310.1148/rycan.2020190083 33778723
     [Google Scholar]
  113. SantagataS. EberlinL.S. NortonI. CalligarisD. FeldmanD.R. IdeJ.L. LiuX. WileyJ.S. VestalM.L. RamkissoonS.H. OrringerD.A. GillK.K. DunnI.F. Dias-SantagataD. LigonK.L. JoleszF.A. GolbyA.J. CooksR.G. AgarN.Y.R. Intraoperative mass spectrometry mapping of an onco-metabolite to guide brain tumor surgery.Proc. Natl. Acad. Sci. USA201411130111211112610.1073/pnas.1404724111 24982150
     [Google Scholar]
  114. PekovS.I. BormotovD.S. BocharovaS.I. SorokinA.A. DerkachM.M. PopovI.A. Mass spectrometry for neurosurgery: Intraoperative support in decision‐making.Mass Spectrom. Rev.2024mas.2188310.1002/mas.21883 38571445
     [Google Scholar]
  115. MoratoN.M. BrownH.M. GarciaD. MiddlebrooksE.H. JentoftM. ChaichanaK. Quiñones-HinojosaA. CooksR.G. High-throughput analysis of tissue microarrays using automated desorption electrospray ionization mass spectrometry.Sci. Rep.20221211885110.1038/s41598‑022‑22924‑4 36344609
     [Google Scholar]
  116. MausA. FigdoreD. MilosevicD. Algeciras-SchimnichA. BornhorstJ. Comparison of intact protein and digested peptide techniques for high throughput proteotyping of ApoE.Clin. Proteomics20221914210.1186/s12014‑022‑09379‑5 36380282
     [Google Scholar]
/content/journals/ccdt/10.2174/0115680096317314240723054739
Loading
Neomorphic IDH Heterodimer Mutants: An Underestimated Point in Cancer Pathogenesis
Curr. Cancer Drug Targets< 25, 1049 (2025); https://doi.org/10.2174/0115680096317314240723054739
/content/journals/ccdt/10.2174/0115680096317314240723054739
/content/journals/ccdt/10.2174/0115680096317314240723054739
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Cancer; heterodimer mutant; isocitrate dehydrogenase; metabolic reprogramming; metabolism; mutation

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test