Journal Article (Letter)

DKFZ-2021-02775

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png High-Resolution Cartography of the Transcriptome and Methylome Landscapes of Diffuse Gliomas.

Willscher, E.Extern* ; Hopp, L. ; Kreuz, M. ; Schmidt, M. ; Hakobyan, S. ; Arakelyan, A. ; Hentschel, B. ; Jones, D. T. W.DKFZ* ; Pfister, S. M.DKFZ* ; Loeffler, M. ; Loeffler-Wirth, H.Extern* ; Binder, H.Extern*

2021
MDPI Basel

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Please use a persistent id in citations: doi:10.3390/cancers13133198

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.

Keyword(s): DNA methylation ; gene expression ; grade II–IV gliomas ; integrative bioinformatics ; molecular subtypes ; self-organizing maps machine learning ; tumor evolution ; tumor heterogeneity

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Contributing Institute(s):

1. Pediatric Glioma (B360)
2. B062 Pädiatrische Neuroonkologie (B062)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2021

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