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

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Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma. / Drexler, Richard; Khatri, Robin; Schüller, Ulrich; Eckhardt, Alicia; Ryba, Alice; Sauvigny, Thomas; Dührsen, Lasse; Mohme, Malte; Ricklefs, Tammo; Bode, Helena; Hausmann, Fabian; Huber, Tobias B; Bonn, Stefan; Voß, Hannah; Neumann, Julia E; Silverbush, Dana; Hovestadt, Volker; Suvà, Mario L; Lamszus, Katrin; Gempt, Jens; Westphal, Manfred; Heiland, Dieter H; Hänzelmann, Sonja; Ricklefs, Franz L.

In: ACTA NEUROPATHOL, Vol. 147, No. 1, 20.01.2024, p. 21.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

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, 'Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma', ACTA NEUROPATHOL, vol. 147, no. 1, pp. 21. https://doi.org/10.1007/s00401-023-02677-8

APA

Drexler, R., Khatri, R., Schüller, U., Eckhardt, A., Ryba, A., Sauvigny, T., Dührsen, L., Mohme, M., Ricklefs, T., Bode, H., Hausmann, F., Huber, T. B., Bonn, S., Voß, H., Neumann, J. E., Silverbush, D., Hovestadt, V., Suvà, M. L., Lamszus, K., ... Ricklefs, F. L. (2024). Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma. ACTA NEUROPATHOL, 147(1), 21. https://doi.org/10.1007/s00401-023-02677-8

Vancouver

Drexler R, Khatri R, Schüller U, Eckhardt A, Ryba A, Sauvigny T et al. Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma. ACTA NEUROPATHOL. 2024 Jan 20;147(1):21. https://doi.org/10.1007/s00401-023-02677-8

Bibtex

@article{b98893cf119542ad94a90d5fe7177ab6,
title = "Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma",
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.",
keywords = "Humans, Glioblastoma/genetics, DNA Methylation, Neoplasm Recurrence, Local/genetics, Survival Analysis, Brain Neoplasms",
author = "Richard Drexler and Robin Khatri and Ulrich Sch{\"u}ller and Alicia Eckhardt and Alice Ryba and Thomas Sauvigny and Lasse D{\"u}hrsen and Malte Mohme and Tammo Ricklefs and Helena Bode and Fabian Hausmann and Huber, {Tobias B} and Stefan Bonn and Hannah Vo{\ss} and Neumann, {Julia E} and Dana Silverbush and Volker Hovestadt and Suv{\`a}, {Mario L} and Katrin Lamszus and Jens Gempt and Manfred Westphal and Heiland, {Dieter H} and Sonja H{\"a}nzelmann and Ricklefs, {Franz L}",
note = "{\textcopyright} 2024. The Author(s).",
year = "2024",
month = jan,
day = "20",
doi = "10.1007/s00401-023-02677-8",
language = "English",
volume = "147",
pages = "21",
journal = "ACTA NEUROPATHOL",
issn = "0001-6322",
publisher = "Springer",
number = "1",

}

RIS

TY - JOUR

T1 - Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma

AU - Drexler, Richard

AU - Khatri, Robin

AU - Schüller, Ulrich

AU - Eckhardt, Alicia

AU - Ryba, Alice

AU - Sauvigny, Thomas

AU - Dührsen, Lasse

AU - Mohme, Malte

AU - Ricklefs, Tammo

AU - Bode, Helena

AU - Hausmann, Fabian

AU - Huber, Tobias B

AU - Bonn, Stefan

AU - Voß, Hannah

AU - Neumann, Julia E

AU - Silverbush, Dana

AU - Hovestadt, Volker

AU - Suvà, Mario L

AU - Lamszus, Katrin

AU - Gempt, Jens

AU - Westphal, Manfred

AU - Heiland, Dieter H

AU - Hänzelmann, Sonja

AU - Ricklefs, Franz L

N1 - © 2024. The Author(s).

PY - 2024/1/20

Y1 - 2024/1/20

N2 - 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.

AB - 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.

KW - Humans

KW - Glioblastoma/genetics

KW - DNA Methylation

KW - Neoplasm Recurrence, Local/genetics

KW - Survival Analysis

KW - Brain Neoplasms

U2 - 10.1007/s00401-023-02677-8

DO - 10.1007/s00401-023-02677-8

M3 - SCORING: Journal article

C2 - 38244080

VL - 147

SP - 21

JO - ACTA NEUROPATHOL

JF - ACTA NEUROPATHOL

SN - 0001-6322

IS - 1

ER -