Journal Article DKFZ-2022-03015

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Systematic multi-omics cell line profiling uncovers principles of Ewing sarcoma fusion oncogene-mediated gene regulation.

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2022
Elsevier [New York, NY]

Cell reports 41(10), 111761 () [10.1016/j.celrep.2022.111761]
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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.

Keyword(s): CP: Cancer ; ChiP-seq ; EWSR1-ERG ; EWSR1-ETS ; EWSR1-FLI1 ; Ewing sarcoma ; enhancer ; microsatellites ; multi-omics ; pediatric sarcoma ; tumor heterogeneity

Classification:

Note: #LA:B410#

Contributing Institute(s):
  1. Translationale Pädiatrische Sarkomforschung (B410)
  2. DKTK HD zentral (HD01)
  3. B062 Pädiatrische Neuroonkologie (B062)
  4. DKTK MU LMU zentral (MU01)
Research Program(s):
  1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2022
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Medline ; DOAJ ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2022-12-12, last modified 2024-02-29



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