IDH mutation
IDH mutation is a re-occuring theme in molecular neuropathology. IDH is an oncometabolite. Mutations are located at hotspot positions in IDH R132, IDH2 R140 or IDH2 R172.[1] [2]
General
Seen in:[3]
- Astrocytoma.
- Oligodendroglioma (requirement for diagnosis).
- Secondary Glioblastoma.
Less common:
Molecular background
- IDH are present as homodimers and oxidize isocitrate to alpha-ketoglutarate.
- Heterozygous IDH mutations result in reduction of alpha-ketoglutrate to D-2-hydroxyglutarate.
- D-2-hydroxyglutarate blocks histone demethylation and promotes proliferation.
- The increased D-2-hydroxyglutarate can be detected by Proton magnetic resonance spectroscopy.[7]
Implication
- IDH mutant gliomas have a more favourable outcome than wildtype tumors[8]
- Within IDH mutant tumors, conventional grading is not represented by diffent survival.[9]
- IDH1 and IDH2 mutations are mutually exclusive.
- IDH2 mutations are more common in oligodendroglial tumors.
Diagnosis
- (Pyro)sequencing of exon4 IDH1/2
- Mutation-specific antibody for the most common IDH-1 R132H mutation available.
- IDH1 mutations are far more common than IDH2 mutations in glioma.
See also
References
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 147700
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 147650
- ↑ Capper, D.; Reuss, D.; Schittenhelm, J.; Hartmann, C.; Bremer, J.; Sahm, F.; Harter, PN.; Jeibmann, A. et al. (Feb 2011). "Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma-like morphology.". Acta Neuropathol 121 (2): 241-52. doi:10.1007/s00401-010-0770-2. PMID 21069360.
- ↑ Andrulis, M.; Capper, D.; Luft, T.; Hartmann, C.; Zentgraf, H.; von Deimling, A. (Aug 2010). "Detection of isocitrate dehydrogenase 1 mutation R132H in myelodysplastic syndrome by mutation-specific antibody and direct sequencing.". Leuk Res 34 (8): 1091-3. doi:10.1016/j.leukres.2010.02.014. PMID 20227112.
- ↑ Zou, S.; Li, J.; Zhou, H.; Frech, C.; Jiang, X.; Chu, JS.; Zhao, X.; Li, Y. et al. (Dec 2014). "Mutational landscape of intrahepatic cholangiocarcinoma.". Nat Commun 5: 5696. doi:10.1038/ncomms6696. PMID 25526346.
- ↑ Capper, D.; Engel, NW.; Stichel, D.; Lechner, M.; Glöss, S.; Schmid, S.; Koelsche, C.; Schrimpf, D. et al. (08 2018). "DNA methylation-based reclassification of olfactory neuroblastoma.". Acta Neuropathol 136 (2): 255-271. doi:10.1007/s00401-018-1854-7. PMID 29730775.
- ↑ Choi, C.; Raisanen, JM.; Ganji, SK.; Zhang, S.; McNeil, SS.; An, Z.; Madan, A.; Hatanpaa, KJ. et al. (Nov 2016). "Prospective Longitudinal Analysis of 2-Hydroxyglutarate Magnetic Resonance Spectroscopy Identifies Broad Clinical Utility for the Management of Patients With IDH-Mutant Glioma.". J Clin Oncol 34 (33): 4030-4039. doi:10.1200/JCO.2016.67.1222. PMID 28248126.
- ↑ Hartmann, C.; Hentschel, B.; Wick, W.; Capper, D.; Felsberg, J.; Simon, M.; Westphal, M.; Schackert, G. et al. (Dec 2010). "Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas.". Acta Neuropathol 120 (6): 707-18. doi:10.1007/s00401-010-0781-z. PMID 21088844.
- ↑ Reuss, DE.; Mamatjan, Y.; Schrimpf, D.; Capper, D.; Hovestadt, V.; Kratz, A.; Sahm, F.; Koelsche, C. et al. (Jun 2015). "IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO.". Acta Neuropathol 129 (6): 867-73. doi:10.1007/s00401-015-1438-8. PMID 25962792.