Proteomics separates adult-type diffuse high-grade gliomas in metabolic subgroups independent of 1p/19q codeletion and across IDH mutational status

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  • Jakob Maximilian Bader
  • Nikolaus Deigendesch
  • Martin Misch
  • Mann, Matthias
  • Arend Koch
  • Felix Meissner

High-grade adult-type diffuse gliomas are malignant neuroepithelial tumors with poor survival rates in combined chemoradiotherapy. The current WHO classification is based on IDH1/2 mutational and 1p/19q codeletion status. Glioma proteome alterations remain undercharacterized despite their promise for a better molecular patient stratification and therapeutic target identification. Here, we use mass spectrometry to characterize 42 formalin-fixed, paraffin-embedded (FFPE) samples from IDH-wild-type (IDHwt) gliomas, IDH-mutant (IDHmut) gliomas with and without 1p/19q codeletion, and non-neoplastic controls. Based on more than 5,500 quantified proteins and 5,000 phosphosites, gliomas separate by IDH1/2 mutational status but not by 1p/19q status. Instead, IDHmut gliomas split into two proteomic subtypes with widespread perturbations, including aerobic/anaerobic energy metabolism. Validations with three independent glioma proteome datasets confirm these subgroups and link the IDHmut subtypes to the established proneural and classic/mesenchymal subtypes in IDHwt glioma. This demonstrates common phenotypic subtypes across the IDH status with potential therapeutic implications for patients with IDHmut gliomas.

Original languageEnglish
Article number100877
JournalCell Reports Medicine
Volume4
Issue number1
ISSN2666-3791
DOIs
Publication statusPublished - 2023

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Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

ID: 331589871