gms | German Medical Science

73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

29.05. - 01.06.2022, Köln

DNA Methylation subclass Receptor Tyrosine Kinase II (RTK II) is predictive for seizure development in glioblastoma patients

DNA Methylierungsklasse Rezeptor-Tyrosinkinase II (RTK II) ist ein Prädiktor für die Entwicklung von tumorassoziierter Epilepsie bei Glioblastom-Patienten

Meeting Abstract

  • presenting/speaker Richard Drexler - Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
  • Franz Lennard Ricklefs - Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
  • Kathrin Wollmann - Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
  • Alicia Eckhardt - Universitätsklinikum Hamburg-Eppendorf, Institut für Neuropathologie, Hamburg, Deutschland
  • Dieter Henrik Heiland - Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland
  • Thomas Sauvigny - Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
  • Ulrich Schüller - Universitätsklinikum Hamburg-Eppendorf, Institut für Neuropathologie, Hamburg, Deutschland
  • Lasse Dührsen - Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie. Köln, 29.05.-01.06.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocV005

doi: 10.3205/22dgnc005, urn:nbn:de:0183-22dgnc0050

Published: May 25, 2022

© 2022 Drexler et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objective: Seizures can present at any time before or after the diagnosis of a glioma. Roughly, 25-30 % of glioblastoma (GBM) patients initially present with seizures, and an additional 30 % develop seizures during the course of the disease. Early studies failed to show an effect of general administration of anti-epileptic drugs for glioblastoma patients, since they were unable to stratify patients into high- or low-risk seizure groups.

Methods: 112 patients, who underwent surgery for a GBM, were included. Genome-wide DNA methylation profiling was performed, before methylation subclasses and copy number changes inferred from methylation data were correlated with clinical characteristics. Independently, global gene expression was analyzed in GBM methylation subclasses from TCGA datasets (n=68).

Results: Receptor tyrosine Kinase (RTK) II GBM showed a significantly higher incidence of seizures than RTK I and mesenchymal (MES) GBM (p<0.01). Accordingly, RNA expression datasets revealed an upregulation of genes involved in neurotransmitter synapses and vesicle transport in RTK II glioblastomas. In a multivariate analysis, temporal location (p=0.01, OR 6.35) and RTK II (p=0.03, OR 5.56) were most predictive for preoperative seizures. During postoperative follow-up, only RTK II remained significantly associated with the development of seizures (p<0.01, OR 8.23). Consequently, the need for antiepileptic medication and its increase due to treatment failure was highly associated with the RTK II methylation subclass (p<0.01).

Conclusion: Our study shows a strong correlation of RTK II glioblastomas with preoperative and long-term seizures. These results underline the benefit of molecular glioblastoma profiling with important implications for postoperative seizure control.

Figure 1 [Fig. 1]