Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma
Drexler R, Khatri R, Schüller U, Eckhardt A, Ryba A, Sauvigny T, Dührsen L, Mohme M, Ricklefs T, Bode H, Hausmann F, Huber TB, Bonn S, Voß H, Neumann JE, Silverbush D, Hovestadt V, Suvà ML, Lamszus K, Gempt J, Westphal M, Heiland DH, Hänzelmann S, Ricklefs FL (2024)
Publication Type: Journal article
Publication year: 2024
Journal
Book Volume: 147
Article Number: 21
Journal Issue: 1
DOI: 10.1007/s00401-023-02677-8
Abstract
The longitudinal transition of phenotypes is pivotal in glioblastoma treatment resistance and DNA methylation emerged as an important tool for classifying glioblastoma phenotypes. We aimed to characterize DNA methylation subclass heterogeneity during progression and assess its clinical impact. Matched tissues from 47 glioblastoma patients were subjected to DNA methylation profiling, including CpG-site alterations, tissue and serum deconvolution, mass spectrometry, and immunoassay. Effects of clinical characteristics on temporal changes and outcomes were studied. Among 47 patients, 8 (17.0%) had non-matching classifications at recurrence. In the remaining 39 cases, 28.2% showed dominant DNA methylation subclass transitions, with 72.7% being a mesenchymal subclass. In general, glioblastomas with a subclass transition showed upregulated metabolic processes. Newly diagnosed glioblastomas with mesenchymal transition displayed increased stem cell-like states and decreased immune components at diagnosis and exhibited elevated immune signatures and cytokine levels in serum. In contrast, tissue of recurrent glioblastomas with mesenchymal transition showed increased immune components but decreased stem cell-like states. Survival analyses revealed comparable outcomes for patients with and without subclass transitions. This study demonstrates a temporal heterogeneity of DNA methylation subclasses in 28.2% of glioblastomas, not impacting patient survival. Changes in cell state composition associated with subclass transition may be crucial for recurrent glioblastoma targeted therapies.
Involved external institutions
Universitätsklinikum Freiburg
Germany (DE)
Universitätsklinikum Hamburg-Eppendorf (UKE)
Germany (DE)
Kinderkrebs-Zentrum Hamburg gGmbH
Germany (DE)
Eli and Edythe L. Broad Institute of MIT and Harvard
United States (USA) (US)
Germany (DE)
Universitätsklinikum Hamburg-Eppendorf (UKE)
Germany (DE)
Kinderkrebs-Zentrum Hamburg gGmbH
Germany (DE)
Eli and Edythe L. Broad Institute of MIT and Harvard
United States (USA) (US)
How to cite
APA:
Drexler, R., Khatri, R., Schüller, U., Eckhardt, A., Ryba, A., Sauvigny, T.,... Ricklefs, F.L. (2024). Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma. Acta Neuropathologica, 147(1). https://doi.org/10.1007/s00401-023-02677-8
MLA:
Drexler, Richard, et al. "Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma." Acta Neuropathologica 147.1 (2024).
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