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. 2020 Nov;146(11):2885-2896.
doi: 10.1007/s00432-020-03349-w. Epub 2020 Aug 10.

DNA CpG methylation in sequential glioblastoma specimens

Zoltan Kraboth  1   2 , Bence Galik  2   3 , Marton Tompa  1   2 , Bela Kajtar  4 , Peter Urban  2 , Attila Gyenesei  2   3 , Attila Miseta  1 , Bernadette Kalman  5   6
Affiliations

DNA CpG methylation in sequential glioblastoma specimens

Zoltan Kraboth et al. J Cancer Res Clin Oncol. 2020 Nov.

Abstract

Purpose: Glioblastoma is the most aggressive form of brain tumors. A better understanding of the molecular mechanisms leading to its evolution is essential for the development of treatments more effective than the available modalities. Here, we aim to identify molecular drivers of glioblastoma development and recurrence by analyzing DNA CpG methylation patterns in sequential samples.

Methods: DNA was isolated from 22 pairs of primary and recurrent formalin-fixed, paraffin-embedded glioblastoma specimens, and subjected to reduced representation bisulfite sequencing. Bioinformatic analyses were conducted to identify differentially methylated sites and pathways, and biostatistics was used to test correlations among clinical and pathological parameters.

Results: Differentially methylated pathways likely involved in primary tumor development included those of neuronal differentiation, myelination, metabolic processes, synapse organization and endothelial cell proliferation, while pathways differentially active during glioblastoma recurrence involved those associated with cell processes and differentiation, immune response, Wnt regulation and catecholamine secretion and transport.

Conclusion: DNA CpG methylation analyses in sequential clinical specimens revealed hypomethylation in certain pathways such as neuronal tissue development and angiogenesis likely involved in early tumor development and growth, while suggested altered regulation in catecholamine secretion and transport, Wnt expression and immune response contributing to glioblastoma recurrence. These pathways merit further investigations and may represent novel therapeutic targets.

Keywords: DNA CpG methylation; Gene ontology analyses; Glioblastoma; Progression; Tumorigenesis.

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Conflict of interest statement

The authors declare that they have no financial or professional conflict of interest related to this study.

Figures

Fig. 1
Fig. 1
Mechanisms of GBM development and recurrence revealed by DNA CpG methylation. This figure provides a schematic depiction of molecular pathways and potential mechanisms contributing to GBM development and recurrence as revealed by RRBS and NGS of sequential GBM specimens
See this image and copyright information in PMC

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