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@ARTICLE{Willscher:177734,
author = {E. Willscher and L. Hopp and M. Kreuz and M. Schmidt and S.
Hakobyan and A. Arakelyan and B. Hentschel and D. T. W.
Jones$^*$ and S. M. Pfister$^*$ and M. Loeffler and H.
Loeffler-Wirth and H. Binder},
title = {{H}igh-{R}esolution {C}artography of the {T}ranscriptome
and {M}ethylome {L}andscapes of {D}iffuse {G}liomas.},
journal = {Cancers},
volume = {13},
number = {13},
issn = {2072-6694},
address = {Basel},
publisher = {MDPI},
reportid = {DKFZ-2021-02775},
pages = {3198},
year = {2021},
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.},
subtyp = {Letter},
keywords = {DNA methylation (Other) / gene expression (Other) / grade
II–IV gliomas (Other) / integrative bioinformatics (Other)
/ molecular subtypes (Other) / self-organizing maps machine
learning (Other) / tumor evolution (Other) / tumor
heterogeneity (Other)},
cin = {B360 / B062},
ddc = {610},
cid = {I:(DE-He78)B360-20160331 / I:(DE-He78)B062-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34206856},
pmc = {pmc:PMC8268631},
doi = {10.3390/cancers13133198},
url = {https://inrepo02.dkfz.de/record/177734},
}