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

Autor:	Orth MF; Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, 80337 Munich, Germany., Surdez D; INSERM Unit 830 'Genetics and Biology of Cancers,' Institut Curie Research Center, 75005 Paris, France; Balgrist University Hospital, Faculty of Medicine, University of Zürich, 8008 Zürich, Switzerland., Faehling T; Hopp Children's Cancer Center (KiTZ), 69120 Heidelberg, Germany; Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany., Ehlers AC; Hopp Children's Cancer Center (KiTZ), 69120 Heidelberg, Germany; Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany., Marchetto A; Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, 80337 Munich, Germany., Grossetête S; INSERM Unit 830 'Genetics and Biology of Cancers,' Institut Curie Research Center, 75005 Paris, France., Volckmann R; Department of Oncogenomics, Amsterdam University Medical Centers (AUMC), 1105 Amsterdam, the Netherlands., Zwijnenburg DA; Department of Oncogenomics, Amsterdam University Medical Centers (AUMC), 1105 Amsterdam, the Netherlands., Gerke JS; Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, 80337 Munich, Germany., Zaidi S; INSERM Unit 830 'Genetics and Biology of Cancers,' Institut Curie Research Center, 75005 Paris, France., Alonso J; Unidad de Tumores Sólidos Infantiles, Instituto de Investigación de Enfermedades Raras, Instituto de Salud Carlos III, 28029 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CB06/07/1009, CIBERER-ISCIII), 28029 Madrid, Spain., Sastre A; Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, 28029 Madrid, Spain., Baulande S; Institut Curie Genomics of Excellence (ICGex) Platform, Institut Curie Research Center, 75005 Paris, France., Sill M; Hopp Children's Cancer Center (KiTZ), 69120 Heidelberg, Germany; Division of Pediatric Neuro-Oncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany., Cidre-Aranaz F; Hopp Children's Cancer Center (KiTZ), 69120 Heidelberg, Germany; Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany., Ohmura S; Hopp Children's Cancer Center (KiTZ), 69120 Heidelberg, Germany; Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany., Kirchner T; Institute of Pathology, Faculty of Medicine, LMU Munich, 80337 Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, 80337 Munich, Germany; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Hauck SM; Research Unit Protein Science and Metabolomics and Proteomics Core, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany., Reischl E; Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany., Gymrek M; Division of Genetics, Department of Medicine, University of California, San Diego, San Diego, CA 92093, USA; Department of Computer Science and Engineering, University of California, San Diego, San Diego, CA 92093, USA., Pfister SM; Hopp Children's Cancer Center (KiTZ), 69120 Heidelberg, Germany; Division of Pediatric Neuro-Oncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; Department of Pediatric Hematology & Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany., Strauch K; Institute of Medical Biometry, Epidemiology, and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany; Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany; Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Faculty of Medicine, LMU Munich, 81377 Munich, Germany., Koster J; Department of Oncogenomics, Amsterdam University Medical Centers (AUMC), 1105 Amsterdam, the Netherlands., Delattre O; INSERM Unit 830 'Genetics and Biology of Cancers,' Institut Curie Research Center, 75005 Paris, France., Grünewald TGP; Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, 80337 Munich, Germany; Hopp Children's Cancer Center (KiTZ), 69120 Heidelberg, Germany; Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany. Electronic address: t.gruenewald@dkfz-heidelberg.de.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Dec 06; Vol. 41 (10), pp. 111761.
DOI:	10.1016/j.celrep.2022.111761
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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