Home > A. Molecular pathology > IDH1

IDH1

Thursday 2 September 2010

Immunochemistry

Differentiation of gliomas and reactive gliosis may be challenging both at primary tumor occurrence and at posttherapy biopsy.

The most frequent IDH1 mutation found in the majority of WHO grade II and III gliomas can be visualized with an antibody specifically detecting mutant IDH1 protein.

mIDH1R132H is a tumor-specific marker that is superior to other established markers to differentiate reactive from neoplastic cells in grade II and III gliomas and allows identifying tumor cells in posttherapy specimens with extensive reactive changes.

As IDH mutations are not characteristic of grade IV primary glioblastomas, this antibody cannot differentiate primary glioblastoma from reactive gliosis. Thus, caution has to be taken and a combined panel with other markers is needed.

Pathology

- Somatic mosaic IDH1 and IDH2 mutations in:

  • malignant gliomas (#20725730#)
  • melanoma (#20603105#)
  • enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome (#22057234#)

See also

- IDHs
- IDH2
- IDH1-associated malignant gliomas

References

- Pyrosequencing of IDH1 and IDH2 Mutations in Brain Tumors and Non-neoplastic Conditions. Cykowski MD, Allen RA, Fung KM, Harmon MA, Dunn ST. Diagn Mol Pathol. 2012 Dec;21(4):214-20. doi: 10.1097/PDM.0b013e31825d802b. PMID: #23111198#

- Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. Pansuriya TC, van Eijk R, d’Adamo P, van Ruler MA, Kuijjer ML, Oosting J, Cleton-Jansen AM, van Oosterwijk JG, Verbeke SL, Meijer D, van Wezel T, Nord KH, Sangiorgi L, Toker B, Liegl-Atzwanger B, San-Julian M, Sciot R, Limaye N, Kindblom LG, Daugaard S, Godfraind C, Boon LM, Vikkula M, Kurek KC, Szuhai K, French PJ, Bovée JV. Nat Genet. 2011 Nov 6. PMID: #22057234#

- IDH1 mutations are common in malignant gliomas arising in adolescents: a report from the Children’s Oncology Group. Pollack IF, Hamilton RL, Sobol RW, Nikiforova MN, Lyons-Weiler MA, Laframboise WA, Burger PC, Brat DJ, Rosenblum MK, Holmes EJ, Zhou T, Jakacki RI; for the Children’s Oncology Group. Childs Nerv Syst. 2010 Aug 20. PMID: #20725730#

- Application of mutant IDH1 antibody to differentiate diffuse glioma from nonneoplastic central nervous system lesions and therapy-induced changes. Capper D, Sahm F, Hartmann C, Meyermann R, von Deimling A, Schittenhelm J. Am J Surg Pathol. 2010 Aug;34(8):1199-204. PMID: #20661018#

- Isocitrate dehydrogenase-1 mutations: a fundamentally new understanding of diffuse glioma? Kloosterhof NK, Bralten LB, Dubbink HJ, French PJ, van den Bent MJ. Lancet Oncol. 2010 Jul 6. PMID: #20615753#

- IDH1 mutation identified in human melanoma. Lopez GY, Reitman ZJ, Solomon D, Waldman T, Bigner DD, McLendon RE, Samuels Y, Yan H. Biochem Biophys Res Commun. 2010 Jul 2. PMID: #20603105#

- Proteomic analysis of hyphae-specific proteins that are expressed differentially in cakem1/cakem1 mutant strains of Candida albicans. Lee KH, Kim SY, Jung JH, Kim J. J Microbiol. 2010 Jun;48(3):365-71. PMID: #20571955#

- 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. Paschka P, Schlenk RF, Gaidzik VI, Habdank M, Krönke J, Bullinger L, Späth D, Kayser S, Zucknick M, Götze K, Horst HA, Germing U, Döhner H, Döhner K. J Clin Oncol. 2010 Jun 21. PMID: #20567020#

- Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia (AML): prevalence and prognostic value. Abbas S, Lugthart S, Kavelaars FG, Schelen A, Koenders J, Zeilemaker A, van Putten WJ, Rijneveld A, Löwenberg B, Valk PJ. Blood. 2010 Jun 10. PMID: #20538800#

- Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism. Reitman ZJ, Yan H. J Natl Cancer Inst. 2010 Jul 7;102(13):932-41. PMID: #20513808#

- Glioma-derived mutations in IDH: from mechanism to potential therapy. Fu Y, Huang R, Du J, Yang R, An N, Liang A. Biochem Biophys Res Commun. 2010 Jun 25;397(2):127-30. PMID: #20510884#

- IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. Tefferi A, Lasho TL, Abdel-Wahab O, Guglielmelli P, Patel J, Caramazza D, Pieri L, Finke CM, Kilpivaara O, Wadleigh M, Mai M, McClure RF, Gilliland DG, Levine RL, Pardanani A, Vannucchi AM. Leukemia. 2010 May 27. PMID: #20508616#

- IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis. Thol F, Weissinger EM, Krauter J, Wagner K, Damm F, Wichmann M, Goehring G, Schumann C, Bug G, Ottmann O, Hofmann WK, Schlegelberger B, Ganser A, Heuser M. Haematologica. 2010 May 21. PMID: #20494930#

- WHO-defined ’myelodysplastic syndrome with isolated del(5q)’ in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations. Patnaik MM, Lasho TL, Finke CM, Gangat N, Caramazza D, Holtan SG, Pardanani A, Knudson RA, Ketterling RP, Chen D, Hoyer JD, Hanson CA, Tefferi A. Leukemia. 2010 May 20. PMID: #20485371#

- Molecular signatures classify astrocytic gliomas by IDH1 mutation status. Toedt G, Barbus S, Wolter M, Felsberg J, Tews B, Blond F, Sabel MC, Hofmann S, Becker N, Hartmann C, Ohgaki H, von Deimling A, Wiestler OD, Hahn M, Lichter P, Reifenberger G, Radlwimmer B. Int J Cancer. 2010 May 12. PMID: #20473936#

- Prognostic markers in gliomas. Labussiere M, Wang XW, Idbaih A, Ducray F, Sanson M. Future Oncol. 2010 May;6(5):733-9. PMID: #20465388#

- Detection of IDH1 and IDH2 mutations by fluorescence melting curve analysis as a diagnostic tool for brain biopsies. Horbinski C, Kelly L, Nikiforov YE, Durso MB, Nikiforova MN. J Mol Diagn. 2010 Jul;12(4):487-92. PMID: #20431032#

- All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2. Labussière M, Idbaih A, Wang XW, Marie Y, Boisselier B, Falet C, Paris S, Laffaire J, Carpentier C, Crinière E, Ducray F, El Hallani S, Mokhtari K, Hoang-Xuan K, Delattre JY, Sanson M. Neurology. 2010 Jun 8;74(23):1886-90. PMID: #20427748#

- Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia. Thol F, Damm F, Wagner K, Göhring G, Schlegelberger B, Hoelzer D, Lübbert M, Heit W, Kanz L, Schlimok G, Raghavachar A, Fiedler W, Kirchner H, Heil G, Heuser M, Krauter J, Ganser A. Blood. 2010 Apr 26. PMID: #20421455#

- IDH1 and IDH2 mutation analysis in chronic- and blast-phase myeloproliferative neoplasms. Pardanani A, Lasho TL, Finke CM, Mai M, McClure RF, Tefferi A. Leukemia. 2010 Jun;24(6):1146-51. PMID: #20410924#

- Mutations of IDH1 and IDH2 genes in early and accelerated phases of myelodysplastic syndromes and MDS/myeloproliferative neoplasms. Kosmider O, Gelsi-Boyer V, Slama L, Dreyfus F, Beyne-Rauzy O, Quesnel B, Hunault-Berger M, Slama B, Vey N, Lacombe C, Solary E, Birnbaum D, Bernard OA, Fontenay M. Leukemia. 2010 May;24(5):1094-6. PMID: #20376084#

- IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Marcucci G, Maharry K, Wu YZ, Radmacher MD, Mrózek K, Margeson D, Holland KB, Whitman SP, Becker H, Schwind S, Metzeler KH, Powell BL, Carter TH, Kolitz JE, Wetzler M, Carroll AJ, Baer MR, Caligiuri MA, Larson RA, Bloomfield CD. J Clin Oncol. 2010 May 10;28(14):2348-55. PMID: #20368543#

- IDH1 and IDH2 mutations in gliomas and the associated induction of hypoxia-inducible factor and production of 2-hydroxyglutarate. Komotar RJ, Starke RM, Sisti MB, Connolly ES. Neurosurgery. 2010 Apr;66(4):N20-1. PMID: #20305482#

- IDH1 and IDH2: not your typical oncogenes. Reitman ZJ, Parsons DW, Yan H. Cancer Cell. 2010 Mar 16;17(3):215-6. PMID: #20227034#

- Identification and functional characterization of isocitrate dehydrogenase 1 (IDH1) mutations in thyroid cancer. Murugan AK, Bojdani E, Xing M. Biochem Biophys Res Commun. 2010 Mar 12;393(3):555-9. PMID: #20171178#

- The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD, Coller HA, Cross JR, Fantin VR, Hedvat CV, Perl AE, Rabinowitz JD, Carroll M, Su SM, Sharp KA, Levine RL, Thompson CB. Cancer Cell. 2010 Mar 16;17(3):225-34. PMID: #20171147#

- IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. van den Bent MJ, Dubbink HJ, Marie Y, Brandes AA, Taphoorn MJ, Wesseling P, Frenay M, Tijssen CC, Lacombe D, Idbaih A, van Marion R, Kros JM, Dinjens WN, Gorlia T, Sanson M. Clin Cancer Res. 2010 Mar 1;16(5):1597-604. PMID: #20160062#

- Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. Gross S, Cairns RA, Minden MD, Driggers EM, Bittinger MA, Jang HG, Sasaki M, Jin S, Schenkein DP, Su SM, Dang L, Fantin VR, Mak TW. J Exp Med. 2010 Feb 15;207(2):339-44. PMID: #20142433#

- Rapid and sensitive assessment of the IDH1 and IDH2 mutation status in cerebral gliomas based on DNA pyrosequencing. Felsberg J, Wolter M, Seul H, Friedensdorf B, Göppert M, Sabel MC, Reifenberger G. Acta Neuropathol. 2010 Apr;119(4):501-7. PMID: #20131059#

- Mutations of the metabolic genes IDH1, IDH2, and SDHAF2 are not major determinants of the pseudohypoxic phenotype of sporadic pheochromocytomas and paragangliomas. Yao L, Barontini M, Niederle B, Jech M, Pfragner R, Dahia PL. J Clin Endocrinol Metab. 2010 Mar;95(3):1469-72. PMID: #20130071#

- Somatic mutations of IDH1 and IDH2 in the leukemic transformation of myeloproliferative neoplasms. Green A, Beer P. N Engl J Med. 2010 Jan 28;362(4):369-70. PMID: #20107228#

- Mutant metabolic enzymes are at the origin of gliomas. Yan H, Bigner DD, Velculescu V, Parsons DW. Cancer Res. 2009 Dec 15;69(24):9157-9. PMID: #19996293#

- IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide. Dubbink HJ, Taal W, van Marion R, Kros JM, van Heuvel I, Bromberg JE, Zonnenberg BA, Zonnenberg CB, Postma TJ, Gijtenbeek JM, Boogerd W, Groenendijk FH, Smitt PA, Dinjens WN, van den Bent MJ. Neurology. 2009 Nov 24;73(21):1792-5. PMID: #19933982#

- Diagnostic use of IDH1/2 mutation analysis in routine clinical testing of formalin-fixed, paraffin-embedded glioma tissues. Horbinski C, Kofler J, Kelly LM, Murdoch GH, Nikiforova MN. J Neuropathol Exp Neurol. 2009 Dec;68(12):1319-25.PMID: #19915484# 31.

- Isocitrate dehydrogenase mutations are rare in pheochromocytomas and paragangliomas. Gaal J, Burnichon N, Korpershoek E, Roncelin I, Bertherat J, Plouin PF, de Krijger RR, Gimenez-Roqueplo AP, Dinjens WN. J Clin Endocrinol Metab. 2010 Mar;95(3):1274-8. PMID: #19915015#

- IDH1 and IDH2 hotspot mutations are not found in canine glioma. Reitman ZJ, Olby NJ, Mariani CL, Thomas R, Breen M, Bigner DD, McLendon RE, Yan H. Int J Cancer. 2010 Jul 1;127(1):245-6. PMID: #19877121#

- Analysis of IDH1 and IDH2 mutations in Japanese glioma patients. Sonoda Y, Kumabe T, Nakamura T, Saito R, Kanamori M, Yamashita Y, Suzuki H, Tominaga T. Cancer Sci. 2009 Oct;100(10):1996-8. PMID: #19765000#

- Novel insights into the pathogenesis of gliomas based on large-scale molecular profiling approaches. Riemenschneider MJ, Reifenberger G. Curr Opin Neurol. 2009 Sep 5. PMID: #19741528#

- Diagnostic and prognostic markers in gliomas. Ducray F, El Hallani S, Idbaih A. Curr Opin Oncol. 2009 Nov;21(6):537-42. PMID: #19667985#

- Advances in the genetics of glioblastoma: are we reaching critical mass? Purow B, Schiff D. Nat Rev Neurol. 2009 Aug;5(8):419-26. PMID: #19597514#

- Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A, Felsberg J, Wolter M, Mawrin C, Wick W, Weller M, Herold-Mende C, Unterberg A, Jeuken JW, Wesseling P, Reifenberger G, von Deimling A. Acta Neuropathol. 2009 Oct;118(4):469-74. PMID: #19554337#

- Combined molecular analysis of BRAF and IDH1 distinguishes pilocytic astrocytoma from diffuse astrocytoma. Korshunov A, Meyer J, Capper D, Christians A, Remke M, Witt H, Pfister S, von Deimling A, Hartmann C. Acta Neuropathol. 2009 Sep;118(3):401-5. PMID: #19543740#

- IDH1 and IDH2 mutations in gliomas. Ducray F, Marie Y, Sanson M. N Engl J Med. 2009 May 21;360(21):2248-9; author reply 2249. PMID: #19469031#

- IDH1 and IDH2 mutations in gliomas. De Carli E, Wang X, Puget S. N Engl J Med. 2009 May 21;360(21):2248; author reply 2249. PMID: #19458374# 42.

- Mutations of IDH1 and IDH2 are not detected in brain metastases of colorectal cancer. Holdhoff M, Parsons DW, Diaz LA Jr. J Neurooncol. 2009 Sep;94(2):297. PMID: #19350208#

- IDH1 and IDH2 mutations in gliomas. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD. N Engl J Med. 2009 Feb 19;360(8):765-73. PMID: #19228619#