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Validation of a methylation-based signature for subventricular zone involvement in glioblastoma

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Title: Validation of a methylation-based signature for subventricular zone involvement in glioblastoma
Authors: Felix Ehret, Oliver Zühlke, Leonille Schweizer, Johannes Kahn, Christoph Csapo-Schmidt, Siyer Roohani, Daniel Zips, David Capper, Sebastian Adeberg, Amir Abdollahi, Maximilian Knoll, David Kaul
Source: J Neurooncol
Publisher Information: Springer Science and Business Media LLC, 2024.
Publication Year: 2024
Subject Terms: 0301 basic medicine, 0303 health sciences, Brain Neoplasms, Research, Intracellular Signaling Peptides and Proteins, Methylation, Methylation [MeSH], Brain Neoplasms/genetics [MeSH], IDH, Humans [MeSH], Prospective Studies [MeSH], Overall survival, Glioblastoma/pathology [MeSH], Subventricular zone, Glioblastoma, Wild type, Adaptor Proteins, Signal Transducing [MeSH], Intracellular Signaling Peptides and Proteins [MeSH], Lateral Ventricles/diagnostic imaging [MeSH], Eye Proteins [MeSH], Brain Neoplasms/diagnostic imaging [MeSH], Glioblastoma/diagnostic imaging [MeSH], Glioblastoma/genetics [MeSH], Lateral Ventricles/pathology [MeSH], Brain Neoplasms/pathology [MeSH], 03 medical and health sciences, Lateral Ventricles, Humans, Prospective Studies, Eye Proteins, Adaptor Proteins, Signal Transducing
Description: Purpose Glioblastomas (GBM) with subventricular zone (SVZ) contact have previously been associated with a specific epigenetic fingerprint. We aim to validate a reported bulk methylation signature to determine SVZ contact. Methods Methylation array analysis was performed on IDHwt GBM patients treated at our institution. The v11b4 classifier was used to ensure the inclusion of only receptor tyrosine kinase (RTK) I, II, and mesenchymal (MES) subtypes. Methylation-based assignment (SVZM ±) was performed using hierarchical cluster analysis. Magnetic resonance imaging (MRI) (T1ce) was independently reviewed for SVZ contact by three experienced readers. Results Sixty-five of 70 samples were classified as RTK I, II, and MES. Full T1ce MRI-based rater consensus was observed in 54 cases, which were retained for further analysis. Epigenetic SVZM classification and SVZ were strongly associated (OR: 15.0, p = 0.003). Thirteen of fourteen differential CpGs were located in the previously described differentially methylated LRBA/MAB21L2 locus. SVZ + tumors were linked to shorter OS (hazard ratio (HR): 3.80, p = 0.02) than SVZM + at earlier time points (time-dependency of SVZM, p Conclusion Herein, we validated the specific epigenetic signature in GBM in the vicinity of the SVZ and highlighted the importance of methylation of a part of the LRBA/MAB21L2 gene locus. Whether SVZM can replace MRI-based SVZ assignment as a prognostic and diagnostic tool will require prospective studies of large, homogeneous cohorts.
Document Type: Article
Other literature type
Language: English
ISSN: 1573-7373
0167-594X
DOI: 10.1007/s11060-024-04570-0
Access URL: https://pubmed.ncbi.nlm.nih.gov/38376766
https://repository.publisso.de/resource/frl:6503738
Rights: CC BY
Accession Number: edsair.doi.dedup.....476e63522649b1e846cf97fbfd2c6d2c
Database: OpenAIRE
Description
Abstract:Purpose Glioblastomas (GBM) with subventricular zone (SVZ) contact have previously been associated with a specific epigenetic fingerprint. We aim to validate a reported bulk methylation signature to determine SVZ contact. Methods Methylation array analysis was performed on IDHwt GBM patients treated at our institution. The v11b4 classifier was used to ensure the inclusion of only receptor tyrosine kinase (RTK) I, II, and mesenchymal (MES) subtypes. Methylation-based assignment (SVZM ±) was performed using hierarchical cluster analysis. Magnetic resonance imaging (MRI) (T1ce) was independently reviewed for SVZ contact by three experienced readers. Results Sixty-five of 70 samples were classified as RTK I, II, and MES. Full T1ce MRI-based rater consensus was observed in 54 cases, which were retained for further analysis. Epigenetic SVZM classification and SVZ were strongly associated (OR: 15.0, p = 0.003). Thirteen of fourteen differential CpGs were located in the previously described differentially methylated LRBA/MAB21L2 locus. SVZ + tumors were linked to shorter OS (hazard ratio (HR): 3.80, p = 0.02) than SVZM + at earlier time points (time-dependency of SVZM, p Conclusion Herein, we validated the specific epigenetic signature in GBM in the vicinity of the SVZ and highlighted the importance of methylation of a part of the LRBA/MAB21L2 gene locus. Whether SVZM can replace MRI-based SVZ assignment as a prognostic and diagnostic tool will require prospective studies of large, homogeneous cohorts.
ISSN:15737373
0167594X
DOI:10.1007/s11060-024-04570-0