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70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

12.05. - 15.05.2019, Würzburg

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Genome-wide methylation profiling of glioblastoma extracellular vesicle DNA allows tumour classifcation

Genomweite Methylierungsprofilierung von extrazellulärem Vesikel DNA bei Glioblastom ermöglicht Tumorklassifizierung

Meeting Abstract

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  • presenting/speaker Franz Lennard Ricklefs - Harvard Medical School, Dept. of Neurosurgery, Boston, MA, United States
  • Cecile Maire - Universitätsklinikum Hamburg-Eppendorf, Neurochirurgie, Hamburg, Deutschland
  • Katharina Kolbe - Universitätsklinikum Hamburg-Eppendorf, Neurochirurgie, Hamburg, Deutschland
  • Mareike Holz - Universitätsklinikum Hamburg-Eppendorf, Neurochirurgie, Hamburg, Deutschland
  • Manfred Westphal - Universitätsklinikum Hamburg-Eppendorf, Neurochirurgie, Hamburg, Deutschland
  • Ulrich Schüller - Universitätsklinikum Hamburg-Eppendorf, Neuropathologie, Hamburg, Deutschland
  • Katrin Lamszus - Universitätsklinikum Hamburg-Eppendorf, Neurochirurgie, Hamburg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie. Würzburg, 12.-15.05.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocP058

doi: 10.3205/19dgnc396, urn:nbn:de:0183-19dgnc3968

Published: May 8, 2019

© 2019 Ricklefs et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: Genome-wide methylation profiling has recently been developed into a tool that allows subtype tumor classification in central nervous system (CNS) tumors. Extracellular vesicles (EVs) are released by CNS tumor cells and contain high molecular weight tumor DNA, rendering EVs a potential biomarker source to identify tumor subgroups, stratify patients and monitor therapy by liquid biopsy. We investigated whether the DNA in glioma-derived EVs reflects genome-wide tumor methylation profiles and allows tumor subtype classification.

Methods: DNA was isolated from EVs secreted by cultured glioma stem-like cells (GSC) as well as from the cells of origin and from the original tumor samples (n=3 patients). EVs were classified by nanoparticle analysis (NTA), immunoblotting, imaging flow cytometry (IFCM), multiplex EV assay and electron microscopy. Genome-wide DNA methylation profiling was performed using a 850k Illumina EPIC array and results were classified according to the DKFZ brain tumor classifier.

Results: The size range of GSC-derived EVs was 120–150 nm, as measured by NTA. The majority of secreted EVs exhibited high expression of common EV markers (i.e. CD9, CD63 and CD81), as characterized by IFCM and multiplex EV assays. Genome-wide methylation profiling of GSC-derived EVs correctly identified the methylation class of the original tumor, including information on the IDH mutation status and subclass classification (RTK1, RTK2). In addition, copy number alterations and the MGMT methylation status matched the pattern of the parental GSCs and original tumor samples.

Conclusion: EV DNA faithfully reflects the tumor methylation class as well as the MGMT methylation status and copy number variations present in the parental cells and the original tumor. Methylation profiling of circulating tumor EV DNA could become a useful tool to detect and classify CNS tumors.