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@ARTICLE{Orth:186218,
author = {M. F. Orth and D. Surdez and T. Faehling$^*$ and A.
Ehlers$^*$ and A. Marchetto and S. Grossetête and R.
Volckmann and D. A. Zwijnenburg and J. S. Gerke and S. Zaidi
and J. Alonso and A. Sastre and S. Baulande and M. Sill$^*$
and F. Cidre-Aranaz$^*$ and S. Ohmura$^*$ and T.
Kirchner$^*$ and S. M. Hauck and E. Reischl and M. Gymrek
and S. Pfister$^*$ and K. Strauch and J. Koster and O.
Delattre and T. Grünewald$^*$},
title = {{S}ystematic multi-omics cell line profiling uncovers
principles of {E}wing sarcoma fusion oncogene-mediated gene
regulation.},
journal = {Cell reports},
volume = {41},
number = {10},
issn = {2211-1247},
address = {[New York, NY]},
publisher = {Elsevier},
reportid = {DKFZ-2022-03015},
pages = {111761},
year = {2022},
note = {#LA:B410#},
abstract = {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.},
keywords = {CP: Cancer (Other) / ChiP-seq (Other) / EWSR1-ERG (Other) /
EWSR1-ETS (Other) / EWSR1-FLI1 (Other) / Ewing sarcoma
(Other) / enhancer (Other) / microsatellites (Other) /
multi-omics (Other) / pediatric sarcoma (Other) / tumor
heterogeneity (Other)},
cin = {B410 / HD01 / B062 / MU01},
ddc = {610},
cid = {I:(DE-He78)B410-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B062-20160331 / I:(DE-He78)MU01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36476851},
doi = {10.1016/j.celrep.2022.111761},
url = {https://inrepo02.dkfz.de/record/186218},
}