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57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

12. - 15.09.2012, Erlangen

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

Association of TET1 nuclear exclusion with loss of 5-hydroxymethylcytosine in IDH1 wild-type gliomas

Meeting Abstract

  • Tim Müller - University of Bonn, Neuropathology, Bonn, Germany
  • presenting/speaker Marco Gessi - University of Bonn, Neuropathology, Bonn, Germany
  • Anke Waha - University of Bonn, Neuropathology, Bonn, Germany
  • Lukas Jan Isselstein - University of Bonn, Neuropathology, Bonn, Germany
  • Daniel Luxen - University of Bonn, Neuropathology, Bonn, Germany
  • Dorothee Freihoff - University of Bonn, Neuropathology, Bonn, Germany
  • Johannes Freihoff - University of Bonn, Neuropathology, Bonn, Germany
  • Albert Becker - University of Bonn, Neuropathology, Bonn, Germany
  • Matthias Simon - University of Bonn, Neurosurgery, Bonn, Germany
  • Jennifer Hammes - University of Bonn, Neuropathology, Bonn, Germany
  • Dorota Denkhaus - University of Bonn, Neuropathology, Bonn, Germany
  • Anja zur Mühlen - University of Bonn, Neuropathology, Bonn, Germany
  • Torsten Pietsch - University of Bonn, Neuropathology, Bonn, Germany
  • Andreas Waha - University of Bonn, Neuropathology, Bonn, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP3.19

DOI: 10.3205/12dgnn063, URN: urn:nbn:de:0183-12dgnn0636

Published: September 11, 2012

© 2012 Müller et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

The identification of isocitrate dehydrogenase 1(IDH1) gene mutations in gliomas inspired various studies exploring the molecular consequences and the clinical implications of such alterations. The Cancer Genome Atlas Research Network uncovered a CpG island methylator phenotype (G-CIMP) in glioblastomas that was associated with IDH1-mutations. Mutant IDH1 protein produces the onco-metabolite 2-hydroxyglutarate that inhibits a-ketoglutarate dependent oxygenases, e.g., TET enzymes involved in the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine. We investigated 60 gliomas for the presence of 5-hydroxymethylcytosine, 5-methylcytosine content, TET1 expression and IDH1 mutation to gain insight into their relationship on the histological level. 61% of gliomas revealed no immunoreactivity for 5-hydroxymethylcytosine and no correlation was observed between IDH1 mutations and loss of 5-hydroxymethylcytosine. Interestingly, expression of TET1 showed remarkable differences with regard to overall protein levels as well as subcellular localization. We found a highly significant (p=0.0007) correlation between IDH1 mutations and nuclear accumulation of TET1 but not with loss of 5hmC. 70% of 5-hydroxymethylcytosine negative gliomas showed either exclusive or dominant cytoplamic expression or no detectable TET1 protein (p=0.0122). Methylation of MGMT and DUSP4/MKP2 was more abundant in gliomas showing nuclear expression of TET1 and harboring mutant IDH1 alleles, but no correlation between global 5-hmC levels and methylation of these genes was observed.

Our data suggest that loss of 5-hydroxymethylcytosine is a frequent event in gliomas independent of IDH1 mutation and may be influenced by nuclear exclusion of TET1 from nuclei of glioma cells.