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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Proteomics separates adult-type diffuse high-grade gliomas in metabolic subgroups independent of 1p/19q codeletion and across IDH mutational status. / Bader, Jakob Maximilian; Deigendesch, Nikolaus; Misch, Martin; Mann, Matthias; Koch, Arend; Meissner, Felix.
In: Cell Reports Medicine, Vol. 4, No. 1, 100877, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Proteomics separates adult-type diffuse high-grade gliomas in metabolic subgroups independent of 1p/19q codeletion and across IDH mutational status
AU - Bader, Jakob Maximilian
AU - Deigendesch, Nikolaus
AU - Misch, Martin
AU - Mann, Matthias
AU - Koch, Arend
AU - Meissner, Felix
N1 - Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1016/j.xcrm.2022.100877
DO - 10.1016/j.xcrm.2022.100877
M3 - Journal article
C2 - 36584682
VL - 4
JO - Cell Reports Medicine
JF - Cell Reports Medicine
SN - 2666-3791
IS - 1
M1 - 100877
ER -
ID: 331589871