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Acta Neuropathologica

, Volume 118, Issue 4, pp 469–474 | Cite as

Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas

  • Christian Hartmann
  • Jochen Meyer
  • Jörg Balss
  • David Capper
  • Wolf Mueller
  • Arne Christians
  • Jörg Felsberg
  • Marietta Wolter
  • Christian Mawrin
  • Wolfgang Wick
  • Michael Weller
  • Christel Herold-Mende
  • Andreas Unterberg
  • Judith W. M. Jeuken
  • Peter Wesseling
  • Guido Reifenberger
  • Andreas von Deimling
Original Paper

Abstract

Somatic mutations in the IDH1 gene encoding cytosolic NADP+-dependent isocitrate dehydrogenase have been shown in the majority of astrocytomas, oligodendrogliomas and oligoastrocytomas of WHO grades II and III. IDH2 encoding mitochondrial NADP+-dependent isocitrate dehydrogenase is also mutated in these tumors, albeit at much lower frequencies. Preliminary data suggest an importance of IDH1 mutation for prognosis showing that patients with anaplastic astrocytomas, oligodendrogliomas and oligoastrocytomas harboring IDH1 mutations seem to fare much better than patients without this mutation in their tumors. To determine mutation types and their frequencies, we examined 1,010 diffuse gliomas. We detected 716 IDH1 mutations and 31 IDH2 mutations. We found 165 IDH1 (72.7%) and 2 IDH2 mutations (0.9%) in 227 diffuse astrocytomas WHO grade II, 146 IDH1 (64.0%) and 2 IDH2 mutations (0.9%) in 228 anaplastic astrocytomas WHO grade III, 105 IDH1 (82.0%) and 6 IDH2 mutations (4.7%) in 128 oligodendrogliomas WHO grade II, 121 IDH1 (69.5%) and 9 IDH2 mutations (5.2%) in 174 anaplastic oligodendrogliomas WHO grade III, 62 IDH1 (81.6%) and 1 IDH2 mutations (1.3%) in 76 oligoastrocytomas WHO grade II and 117 IDH1 (66.1%) and 11 IDH2 mutations (6.2%) in 177 anaplastic oligoastrocytomas WHO grade III. We report on an inverse association of IDH1 and IDH2 mutations in these gliomas and a non-random distribution of the mutation types within the tumor entities. IDH1 mutations of the R132C type are strongly associated with astrocytoma, while IDH2 mutations predominantly occur in oligodendroglial tumors. In addition, patients with anaplastic glioma harboring IDH1 mutations were on average 6 years younger than those without these alterations.

Keywords

IDH1 IDH2 Mutation Glioma Astrocytoma Oligodendroglioma Oligoastrocytoma 

Notes

Acknowledgments

We wish to thank F. Mößler and K. Lindenberg for skillful technical assistance. This work was supported by the Bundesministerium für Bildung und Forschung (BMBF) by a grant to AvD, CH, WW and GR (grant number 01ES0729-30).

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Christian Hartmann
    • 1
    • 2
  • Jochen Meyer
    • 2
  • Jörg Balss
    • 2
  • David Capper
    • 1
  • Wolf Mueller
    • 1
  • Arne Christians
    • 2
  • Jörg Felsberg
    • 3
  • Marietta Wolter
    • 3
  • Christian Mawrin
    • 4
  • Wolfgang Wick
    • 5
  • Michael Weller
    • 6
  • Christel Herold-Mende
    • 7
  • Andreas Unterberg
    • 7
  • Judith W. M. Jeuken
    • 8
  • Peter Wesseling
    • 8
  • Guido Reifenberger
    • 3
  • Andreas von Deimling
    • 1
    • 2
  1. 1.Department of Neuropathology, Institute of PathologyRuprecht-Karls-Universität HeidelbergHeidelbergGermany
  2. 2.Clinical Cooperation Unit Neuropathology G380German Cancer Research CenterHeidelbergGermany
  3. 3.Department of NeuropathologyHeinrich-Heine-UniversityDüsseldorfGermany
  4. 4.Department of NeuropathologyOtto von Guericke Universität Magdeburg39120MagdeburgGermany
  5. 5.Department of Neurooncology, Clinical Cooperation Unit Neurooncology DKFZRuprecht-Karls-Universität HeidelbergHeidelbergGermany
  6. 6.Department of NeurologyUniversity Hospital ZurichZurichSwitzerland
  7. 7.Department of NeurosurgeryRuprecht-Karls-Universität HeidelbergHeidelbergGermany
  8. 8.Department of PathologyRadboud University Nijmegen Medical CenterNijmegenThe Netherlands

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