TY  - JOUR
AU  - Wu, Yonghe
AU  - Fletcher, Michael
AU  - Gu, Zuguang
AU  - Wang, Qi
AU  - Costa, Barbara Maria
AU  - Bertoni, Anna
AU  - Man, Ka Hou
AU  - Schlotter, Magdalena
AU  - Felsberg, Jörg
AU  - Mangei, Jasmin
AU  - Barbus, Martje
AU  - Gaupel, Ann-Christin
AU  - Wang, Wei
AU  - Weiss, Tobias
AU  - Eils, Roland
AU  - Weller, Michael
AU  - Liu, Haikun
AU  - Reifenberger, Guido
AU  - Korshunov, Andrey
AU  - Angel, Peter
AU  - Lichter, Peter
AU  - Herrmann, Carl
AU  - Radlwimmer, Bernhard
TI  - Glioblastoma epigenome profiling identifies SOX10 as a master regulator of molecular tumour subtype.
JO  - Nature Communications
VL  - 11
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2020-02967
SP  - 6434
PY  - 2020
N1  - #EA:B060#EA:B086#LA:B060# / DKFZ-ZMBH Alliance
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:33339831
DO  - DOI:10.1038/s41467-020-20225-w
UR  - https://inrepo02.dkfz.de/record/166524
ER  -