TY  - JOUR
AU  - Orth, Martin F
AU  - Surdez, Didier
AU  - Faehling, Tobias
AU  - Ehlers, Anna
AU  - Marchetto, Aruna
AU  - Grossetête, Sandrine
AU  - Volckmann, Richard
AU  - Zwijnenburg, Danny A
AU  - Gerke, Julia S
AU  - Zaidi, Sakina
AU  - Alonso, Javier
AU  - Sastre, Ana
AU  - Baulande, Sylvain
AU  - Sill, Martin
AU  - Cidre-Aranaz, Florencia
AU  - Ohmura, Shunya
AU  - Kirchner, Thomas
AU  - Hauck, Stefanie M
AU  - Reischl, Eva
AU  - Gymrek, Melissa
AU  - Pfister, Stefan
AU  - Strauch, Konstantin
AU  - Koster, Jan
AU  - Delattre, Olivier
AU  - Grünewald, Thomas
TI  - Systematic multi-omics cell line profiling uncovers principles of Ewing sarcoma fusion oncogene-mediated gene regulation.
JO  - Cell reports
VL  - 41
IS  - 10
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DKFZ-2022-03015
SP  - 111761
PY  - 2022
N1  - #LA:B410#
AB  - Ewing sarcoma (EwS) is characterized by EWSR1-ETS fusion transcription factors converting polymorphic GGAA microsatellites (mSats) into potent neo-enhancers. Although the paucity of additional mutations makes EwS a genuine model to study principles of cooperation between dominant fusion oncogenes and neo-enhancers, this is impeded by the limited number of well-characterized models. Here we present the Ewing Sarcoma Cell Line Atlas (ESCLA), comprising whole-genome, DNA methylation, transcriptome, proteome, and chromatin immunoprecipitation sequencing (ChIP-seq) data of 18 cell lines with inducible EWSR1-ETS knockdown. The ESCLA shows hundreds of EWSR1-ETS-targets, the nature of EWSR1-ETS-preferred GGAA mSats, and putative indirect modes of EWSR1-ETS-mediated gene regulation, converging in the duality of a specific but plastic EwS signature. We identify heterogeneously regulated EWSR1-ETS-targets as potential prognostic EwS biomarkers. Our freely available ESCLA (http://r2platform.com/escla/) is a rich resource for EwS research and highlights the power of comprehensive datasets to unravel principles of heterogeneous gene regulation by chimeric transcription factors.
KW  - CP: Cancer (Other)
KW  - ChiP-seq (Other)
KW  - EWSR1-ERG (Other)
KW  - EWSR1-ETS (Other)
KW  - EWSR1-FLI1 (Other)
KW  - Ewing sarcoma (Other)
KW  - enhancer (Other)
KW  - microsatellites (Other)
KW  - multi-omics (Other)
KW  - pediatric sarcoma (Other)
KW  - tumor heterogeneity (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36476851
DO  - DOI:10.1016/j.celrep.2022.111761
UR  - https://inrepo02.dkfz.de/record/186218
ER  -