High-Resolution Cartography of the Transcriptome and Methylome Landscapes of Diffuse Gliomas

Abstract:

Molecular mechanisms of lower-grade (II–III) diffuse gliomas (LGG) are still poorly understood, mainly because of their heterogeneity. They split into astrocytoma- (IDH-A) and oligodendroglioma-like (IDH-O) tumors both carrying mutations(s) at the isocitrate dehydrogenase (IDH) gene and into IDH wild type (IDH-wt) gliomas of glioblastoma resemblance. We generated detailed maps of the transcriptomes and DNA methylomes, revealing that cell functions divided into three major archetypic hallmarks: (i) increased proliferation in IDH-wt and, to a lesser degree, IDH-O; (ii) increased inflammation in IDH-A and IDH-wt; and (iii) the loss of synaptic transmission in all subtypes. Immunogenic properties of IDH-A are diverse, partly resembling signatures observed in grade IV mesenchymal glioblastomas or in grade I pilocytic astrocytomas. We analyzed details of coregulation between gene expression and DNA methylation and of the immunogenic micro-environment presumably driving tumor development and treatment resistance. Our transcriptome and methylome maps support personalized, case-by-case views to decipher the heterogeneity of glioma states in terms of data portraits. Thereby, molecular cartography provides a graphical coordinate system that links gene-level information with glioma subtypes, their phenotypes, and clinical context.

SEEK ID: https://armlifebank.am/publications/98

DOI: 10.3390/cancers13133198

Projects: Multi-Omics Molecular Diversity of Cancers

Publication type: Journal

Journal: Cancers

Publisher: MDPI AG

Citation: Cancers,13(13):3198

Date Published: 26th Jun 2021

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Registered Mode: manually

Authors: Edith Willscher, Lydia Hopp, Markus Kreuz, Maria Schmidt, Siras Hakobyan, Arsen Arakelyan, Bettina Hentschel, David T. W. Jones, Stefan M. Pfister, Markus Loeffler, Henry Loeffler-Wirth, Hans Binder

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Willscher, E., Hopp, L., Kreuz, M., Schmidt, M., Hakobyan, S., Arakelyan, A., Hentschel, B., Jones, D. T. W., Pfister, S. M., Loeffler, M., Loeffler-Wirth, H., & Binder, H. (2021). High-Resolution Cartography of the Transcriptome and Methylome Landscapes of Diffuse Gliomas. In Cancers (Vol. 13, Issue 13, p. 3198). MDPI AG. https://doi.org/10.3390/cancers13133198
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Created: 27th Aug 2025 at 11:22

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