%0 Journal Article
%A Willscher, Edith
%A Hopp, Lydia
%A Kreuz, Markus
%A Schmidt, Maria
%A Hakobyan, Siras
%A Arakelyan, Arsen
%A Hentschel, Bettina
%A Jones, David T W
%A Pfister, Stefan M
%A Loeffler, Markus
%A Loeffler-Wirth, Henry
%A Binder, Hans
%T High-Resolution Cartography of the Transcriptome and Methylome Landscapes of Diffuse Gliomas.
%J Cancers
%V 13
%N 13
%@ 2072-6694
%C Basel
%I MDPI
%M DKFZ-2021-02775
%P 3198
%D 2021
%X 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.
%K DNA methylation (Other)
%K gene expression (Other)
%K grade II–IV gliomas (Other)
%K integrative bioinformatics (Other)
%K molecular subtypes (Other)
%K self-organizing maps machine learning (Other)
%K tumor evolution (Other)
%K tumor heterogeneity (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34206856
%2 pmc:PMC8268631
%R 10.3390/cancers13133198
%U https://inrepo02.dkfz.de/record/177734