%0 Journal Article
%A Orth, Martin F
%A Surdez, Didier
%A Faehling, Tobias
%A Ehlers, Anna
%A Marchetto, Aruna
%A Grossetête, Sandrine
%A Volckmann, Richard
%A Zwijnenburg, Danny A
%A Gerke, Julia S
%A Zaidi, Sakina
%A Alonso, Javier
%A Sastre, Ana
%A Baulande, Sylvain
%A Sill, Martin
%A Cidre-Aranaz, Florencia
%A Ohmura, Shunya
%A Kirchner, Thomas
%A Hauck, Stefanie M
%A Reischl, Eva
%A Gymrek, Melissa
%A Pfister, Stefan
%A Strauch, Konstantin
%A Koster, Jan
%A Delattre, Olivier
%A Grünewald, Thomas
%T Systematic multi-omics cell line profiling uncovers principles of Ewing sarcoma fusion oncogene-mediated gene regulation.
%J Cell reports
%V 41
%N 10
%@ 2211-1247
%C [New York, NY]
%I Elsevier
%M DKFZ-2022-03015
%P 111761
%D 2022
%Z #LA:B410#
%X 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.
%K CP: Cancer (Other)
%K ChiP-seq (Other)
%K EWSR1-ERG (Other)
%K EWSR1-ETS (Other)
%K EWSR1-FLI1 (Other)
%K Ewing sarcoma (Other)
%K enhancer (Other)
%K microsatellites (Other)
%K multi-omics (Other)
%K pediatric sarcoma (Other)
%K tumor heterogeneity (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36476851
%R 10.1016/j.celrep.2022.111761
%U https://inrepo02.dkfz.de/record/186218