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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)

A pyrosequencing based identification of histone H3.3 K27M mutations: a diagnostic tool inbrain tumors ofchildhood?

Meeting Abstract

  • presenting/speaker Gerrit H. Gielen - University of Bonn Medical Center, Dept. of Neuropathology, Bonn, Germany
  • Marco Gessi - University of Bonn Medical Center, Dept. of Neuropathology, Bonn, Germany
  • Jennifer Hammes - University of Bonn Medical Center, Dept. of Neuropathology, Bonn, Germany
  • Christof M. Kramm - Martin-Luther-University Halle, University Children's Hospital, Halle, Germany
  • Andreas Waha - University of Bonn Medical Center, Dept. of Neuropathology, Bonn, Germany
  • Torsten Pietsch - University of Bonn Medical Center, Dept. of 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. Doc12dgnnPP3.26

DOI: 10.3205/12dgnn070, URN: urn:nbn:de:0183-12dgnn0701

Published: September 11, 2012

© 2012 Gielen et al.
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Outline

Text

Question: In adult high grade gliomas (HGG) key genetic alterations including IDH1/2 and p53 mutations and EGFR amplification were identified. In contrast, common genetic alterations are largely unknown in pediatric HGG which are considered to differ from adult HGG in their pathogenesis and biological behaviour. Recently, genome-wide sequencing has identified driver mutations in histone H3.3 K27M in 18.75% of pediatric glioblastomas, but not in adult glioblastomas. In this study, we wanted to investigate whether such mutations are specific for pediatric glioblastomas or may occur also in other brain tumor entities.

Methods: We performed a pyro-sequencing based analysis for the incidence of histone H3.3 mutations in 311 pediatric brain tumors, among them 174 diffuse high grade gliomas (127 primary glioblastomas, WHO grade IV (pGBM IV) and 47 anaplastic astrocytomas, WHO grade III). Moreover, 15 pilocytic astrocytomas, 12 desmoplastic infantile gangliogliomas/ astrocytomas, 17 ependymomas, 19 pediatric medulloblastomas, 14 AT/RT, 28 supratentorial CNS-PNETs, 12 ependymoblastomas, 10 gangliogliomas and 10 choroid plexus carcinomas were analysed.

Results: In the 174 pHGG investigated we found in total 43 cases harbouring H3.3 K27M mutations (24.7%). pGBM showed K27M mutations in 33 cases (26%). In addition, 10 of 47 (21.3%) anaplastic astrocytomas also showed K27M mutations. The mean age of the patients carrying mutations was 11.1 years (range 4-18 years), i.e. there was no mutation found in infant cases. All other tumor entities investigated showed no H3.3 K27M mutation at all.

Conclusions: In conclusion, we identified histone H3.3 K27M mutations both in pediatric glioblastomas and in pediatric anaplastic astrocytomas, but not in other investigated brain tumor entities. This indicates that detection of H3.3 K27M mutations may represent a potential diagnostic tool for the differentiation of diffuse high grade astrocytic tumors from other brain tumors in childhood, determinable by pyro-sequencing as a robust and reliable method.