Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma

• DOI: 10.1007/s00401-023-02677-8
• Publication Date: 2024-01-20T14:02:06Z
• Authors: Richard Drexler; Robin Khatri; Ulrich Schüller; Alicia Eckhardt; Alice Ryba; Thomas Sauvigny; Lasse Dührsen; Malte Mohme; Tammo Ricklefs; Helena Bode; Fabian Hausmann; Tobias B. Huber; Stefan Bonn; Hannah Voß; Julia E. Neumann; Dana Silverbush; Volker Hovestadt; Mario L. Suvà; Katrin Lamszus; Jens Gempt; Manfred Westphal; Dieter H. Heiland; Sonja Hänzelmann; Franz L. Ricklefs
• Keywords: Subclass; CpG site

Abstract The longitudinal transition of phenotypes is pivotal in glioblastoma treatment resistance and DNA methylation emerged as an important tool for classifying phenotypes. We aimed to characterize subclass heterogeneity during progression assess its clinical impact. Matched tissues from 47 patients were subjected profiling, including CpG-site alterations, tissue serum deconvolution, mass spectrometry, immunoassay. Effects characteristics on temporal changes outcomes studied. Among patients, 8 (17.0%) had non-matching classifications at recurrence. In the remaining 39 cases, 28.2% showed dominant transitions, with 72.7% being a mesenchymal subclass. general, glioblastomas upregulated metabolic processes. Newly diagnosed displayed increased stem cell-like states decreased immune components diagnosis exhibited elevated signatures cytokine levels serum. contrast, recurrent but states. Survival analyses revealed comparable without transitions. This study demonstrates subclasses glioblastomas, not impacting patient survival. Changes cell state composition associated may be crucial targeted therapies.