TY  - JOUR
AU  - Willscher, Edith
AU  - Hopp, Lydia
AU  - Kreuz, Markus
AU  - Schmidt, Maria
AU  - Hakobyan, Siras
AU  - Arakelyan, Arsen
AU  - Hentschel, Bettina
AU  - Jones, David T W
AU  - Pfister, Stefan M
AU  - Loeffler, Markus
AU  - Loeffler-Wirth, Henry
AU  - Binder, Hans
TI  - High-Resolution Cartography of the Transcriptome and Methylome Landscapes of Diffuse Gliomas.
JO  - Cancers
VL  - 13
IS  - 13
SN  - 2072-6694
CY  - Basel
PB  - MDPI
M1  - DKFZ-2021-02775
SP  - 3198
PY  - 2021
AB  - 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.
KW  - DNA methylation (Other)
KW  - gene expression (Other)
KW  - grade II–IV gliomas (Other)
KW  - integrative bioinformatics (Other)
KW  - molecular subtypes (Other)
KW  - self-organizing maps machine learning (Other)
KW  - tumor evolution (Other)
KW  - tumor heterogeneity (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34206856
C2  - pmc:PMC8268631
DO  - DOI:10.3390/cancers13133198
UR  - https://inrepo02.dkfz.de/record/177734
ER  -