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@ARTICLE{Wu:166524,
author = {Y. Wu$^*$ and M. Fletcher$^*$ and Z. Gu$^*$ and Q. Wang$^*$
and B. M. Costa$^*$ and A. Bertoni$^*$ and K. H. Man$^*$ and
M. Schlotter$^*$ and J. Felsberg and J. Mangei$^*$ and M.
Barbus$^*$ and A.-C. Gaupel$^*$ and W. Wang$^*$ and T. Weiss
and R. Eils$^*$ and M. Weller and H. Liu$^*$ and G.
Reifenberger$^*$ and A. Korshunov$^*$ and P. Angel$^*$ and
P. Lichter$^*$ and C. Herrmann and B. Radlwimmer$^*$},
title = {{G}lioblastoma epigenome profiling identifies {SOX}10 as a
master regulator of molecular tumour subtype.},
journal = {Nature Communications},
volume = {11},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2020-02967},
pages = {6434},
year = {2020},
note = {#EA:B060#EA:B086#LA:B060# / DKFZ-ZMBH Alliance},
abstract = {Glioblastoma frequently exhibits therapy-associated subtype
transitions to mesenchymal phenotypes with adverse
prognosis. Here, we perform multi-omic profiling of 60
glioblastoma primary tumours and use orthogonal analysis of
chromatin and RNA-derived gene regulatory networks to
identify 38 subtype master regulators, whose cell
population-specific activities we further map in published
single-cell RNA sequencing data. These analyses identify the
oligodendrocyte precursor marker and chromatin modifier
SOX10 as a master regulator in RTK I-subtype tumours. In
vitro functional studies demonstrate that SOX10 loss causes
a subtype switch analogous to the proneural-mesenchymal
transition observed in patients at the transcriptomic,
epigenetic and phenotypic levels. SOX10 repression in an in
vivo syngeneic graft glioblastoma mouse model results in
increased tumour invasion, immune cell infiltration and
significantly reduced survival, reminiscent of progressive
human glioblastoma. These results identify SOX10 as a bona
fide master regulator of the RTK I subtype, with both tumour
cell-intrinsic and microenvironmental effects.},
cin = {B060 / B086 / A100 / ED01 / A240 / B300},
ddc = {500},
cid = {I:(DE-He78)B060-20160331 / I:(DE-He78)B086-20160331 /
I:(DE-He78)A100-20160331 / I:(DE-He78)ED01-20160331 /
I:(DE-He78)A240-20160331 / I:(DE-He78)B300-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33339831},
doi = {10.1038/s41467-020-20225-w},
url = {https://inrepo02.dkfz.de/record/166524},
}