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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

MPG-Autoren
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Bader,  Jakob Maximilian
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Mann,  Matthias
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Meissner,  Felix
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Zitation

Bader, J. M., Deigendesch, N., Misch, M., Mann, M., Koch, A., & Meissner, F. (2023). Proteomics separates adult-type diffuse high- grade gliomas in metabolic subgroups independent of 1p/19q codeletion and across IDH mutational status. Cell Reports Medicine, 4(1): 100877. doi:10.1016/j.xcrm.2022.100877.


Zitierlink: https://hdl.handle.net/21.11116/0000-000D-72DD-A
Zusammenfassung
High-grade adult-type diffuse gliomas are malignant neuroepithelial tumors with poor survival rates in com-bined chemoradiotherapy. The current WHO classification is based on IDH1/2 mutational and 1p/19q code-letion status. Glioma proteome alterations remain undercharacterized despite their promise for a better mo-lecular 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 per-turbations, including aerobic/anaerobic energy metabolism. Validations with three independent glioma pro-teome 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.