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

• Verfasst von: Ehret, Felix [VerfasserIn]
• Verfasst von: Zühlke, Oliver [VerfasserIn]
• Verfasst von: Schweizer, Leonille [VerfasserIn]
• Verfasst von: Kahn, Johannes [VerfasserIn]
• Verfasst von: Csapo-Schmidt, Christoph [VerfasserIn]
• Verfasst von: Roohani, Siyer [VerfasserIn]
• Verfasst von: Zips, Daniel [VerfasserIn]
• Verfasst von: Capper, David [VerfasserIn]
• Verfasst von: Adeberg, Sebastian [VerfasserIn]
• Verfasst von: Abdollahi, Amir [VerfasserIn]
• Verfasst von: Knoll, Maximilian [VerfasserIn]
• Verfasst von: Kaul, David [VerfasserIn]
• Titel: Validation of a methylation-based signature for subventricular zone involvement in glioblastoma
• Verf.angabe: 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
• E-Jahr: 2024
• Jahr: 20 February 2024
• Umfang: 9 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 29.08.2024
• Titel Quelle: Enthalten in: Journal of neuro-oncology
• Ort Quelle: Dordrecht [u.a.] : Springer Science + Business Media B.V, 1983
• Jahr Quelle: 2024
• Band/Heft Quelle: 167(2024), 1 vom: März, Seite 89-97
• ISSN Quelle: 1573-7373
• DOI: doi:10.1007/s11060-024-04570-0
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adaptor Proteins, Signal Transducing
• Sach-SW: Brain Neoplasms
• Sach-SW: Eye Proteins
• Sach-SW: Glioblastoma
• Sach-SW: Humans
• Sach-SW: IDH
• Sach-SW: Intracellular Signaling Peptides and Proteins
• Sach-SW: Lateral Ventricles
• Sach-SW: Methylation
• Sach-SW: Overall survival
• Sach-SW: Prospective Studies
• Sach-SW: Subventricular zone
• Sach-SW: Wild type
• K10plus-PPN: 190053469X

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 < 0.05). Considering the SVZ consensus as the ground truth, SVZM classification yields a sensitivity of 96.6%, specificity of 36.0%, positive predictive value (PPV) of 63.6%, and negative predictive value (NPV) of 90.0%. - 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.