Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma.
DNA methylation
Deconvolution
Glioma
Outcome
Subgroup
Temporal
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
20 Jan 2024
20 Jan 2024
Historique:
received:
14
09
2023
accepted:
24
12
2023
revised:
08
12
2023
medline:
20
1
2024
pubmed:
20
1
2024
entrez:
20
1
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38244080
doi: 10.1007/s00401-023-02677-8
pii: 10.1007/s00401-023-02677-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
21Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB 1192 B8
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB 1192 B8
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB 1192 C3
Informations de copyright
© 2024. The Author(s).
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