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Methylation of Ewing sarcoma tumors (ICGC)

ABSTRACT: Ewing sarcoma (ES) is a primary bone tumor initiated by an EWSR1-ETS gene fusion. To characterize the methylation of Ewing sarcoma, reduced representation bisulfite sequencing was performed.

PROVIDER: EGAS00001002161 | EGA |

REPOSITORIES: EGA

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DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma.

Sheffield Nathan C NC Pierron Gaelle G Klughammer Johanna J Datlinger Paul P Schönegger Andreas A Schuster Michael M Hadler Johanna J Surdez Didier D Guillemot Delphine D Lapouble Eve E Freneaux Paul P Champigneulle Jacqueline J Bouvier Raymonde R Walder Diana D Ambros Ingeborg M IM Hutter Caroline C Sorz Eva E Amaral Ana T AT de Álava Enrique E Schallmoser Katharina K Strunk Dirk D Rinner Beate B Liegl-Atzwanger Bernadette B Huppertz Berthold B Leithner Andreas A de Pinieux Gonzague G Terrier Philippe P Laurence Valérie V Michon Jean J Ladenstein Ruth R Holter Wolfgang W Windhager Reinhard R Dirksen Uta U Ambros Peter F PF Delattre Olivier O Kovar Heinrich H Bock Christoph C Tomazou Eleni M EM

Nature medicine 20170130 3

Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genetically homogeneous cancers. We performed genome-scale DNA methylation sequencing for a large cohort of Ewing sarcoma tumors and analyzed epigenetic heterogeneity on three levels: between cancers, between tumors, and within tumors. We observed consistent ...[more]

PMID: 28134926

Similar Datasets

RNA-seq of Ewing sarcoma tumors (ICGC)

Project description:Ewing sarcoma (ES) is a primary bone tumor initiated by an EWSR1-ETS gene fusion. To characterize the transcriptome of Ewing sarcoma, RNA-seq was performed.

| EGAS00001003333 | EGA

Expression profiling of Ewing sarcoma samples

Project description:Expression profiling of Ewing sarcoma samples in the frame of the CIT program from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net). Ewing sarcoma a rare pediatric tumor characterized by EWSR1-ETS fusions, is predominantly observed in populations of European ancestry. A genome-wide association study of at least 401 French ES patients compared to either 684 French or 3668 US self-described Caucasian controls consistently revealed candidate loci at chromosomes 1 and 10 (p<10-6). These loci were further replicated in two independent sets of cases and controls. Joint analysis identified rs9430161 (p=1.4x10-20; OR=2.2, CI99=1.8-2.7) 25kb upstream to TARDBP (1p36.22) and rs224278 (p=4.0x10-17 OR=1.7, CI99=1.4-1.9) 5kb upstream to EGR2 (10q21). The frequency of the major risk haplotypes in the European population were observed to be less prevalent in the African population, suggesting that variants at these loci could contribute to the differences in ES incidence observed between continents. TARDBP shares structural similarities with EWSR1 and FUS (TLS) EGR2 is an EWSR1-ETS target gene. Variants at both loci were associated with expression levels of TARDBP, ADO and EGR2. 117 Ewing sarcoma samples were profiled using affymetrix hgu133Plus2 arrays.

2012-02-11 | E-GEOD-34620 | biostudies-arrayexpress

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

Project description: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.

2024-06-18 | PXD052856 | Pride

Expression profiling of Ewing sarcoma samples

2012-02-11 | GSE34620 | GEO

The Ewing sarcoma cell line atlas (ESCLA) - The relevance of the transcription factors GATA2 and E2F2 in a Ewing sarcoma cell line model

Project description:Cell lines have been essential for major discoveries in cancer including Ewing sarcoma (EwS). EwS is a highly aggressive pediatric bone or soft-tissue cancer characterized by oncogenic EWSR1-ETS fusion transcription factors converting polymorphic GGAA-microsatellites (mSats) into neo-enhancers. However, further detailed mechanistic evaluation of gene regulation in EwS have been hindered by the limited number of well-characterized cell line models. Here, we present the Ewing Sarcoma Cell Line Atlas (ESCLA) comprising 18 EwS cell lines with inducible EWSR1-ETS knockdown that were profiled by whole-genome-sequencing, DNA methylation arrays, gene expression and splicing arrays, mass spectrometry, and ChIP-seq for EWSR1-ETS and histone marks. Systematic analysis of these multi-dimensional data identified GATA2 and E2F2 as EWSR1-ETS-driven putative co-regulatory transcription factors. To evaluate the relevance of these transcrition factors, RNA interference in a Ewing sarcoma cell line was employed with subsequent Affymetrix Exon array profiling. The expression data were analysed in synopsis with the effects of EWSR1-FLI1 in the same cell line.

2022-08-26 | GSE212063 | GEO

The Ewing Sarcoma Cell Line Atlas (ESCLA) - methylation profiling of 18 Ewing sarcoma cell lines in EWSR1-ETS-high versus -low condition

Project description:Cell lines have been essential for major discoveries in cancer including Ewing sarcoma (EwS). EwS is a highly aggressive pediatric bone or soft-tissue cancer characterized by oncogenic EWSR1-ETS fusion transcription factors converting polymorphic GGAA-microsatellites (mSats) into neo-enhancers. However, further detailed mechanistic evaluation of gene regulation in EwS have been hindered by the limited number of well-characterized cell line models. Here, we present the Ewing Sarcoma Cell Line Atlas (ESCLA) comprising 18 EwS cell lines with inducible EWSR1-ETS knockdown that were profiled by whole-genome-sequencing, DNA methylation arrays, gene expression and splicing arrays, mass spectrometry, and ChIP-seq for EWSR1-ETS and histone marks. Systematic analysis of these multi-dimensional data illuminated hundreds of new potential EWSR1-ETS target genes, the nature of EWSR1-ETS-preferred GGAA-mSats, and potential indirect modes of EWSR1-ETS-mediated gene regulation. Moreover, we identified putative co-regulatory transcription factors and heterogeneously regulated EWSR1-ETS target genes that may have implications for the clinical heterogeneity of EwS. Collectively, our freely available ESCLA constitutes an extremely rich resource for EwS research and highlights the power of leveraging multidimensional and comprehensive datasets to unravel principles of heterogeneous gene regulation by dominant fusion oncogenes.

2021-06-09 | GSE176334 | GEO

The Ewing Sarcoma Cell Line Atlas (ESCLA) - expression profiling of 18 Ewing sarcoma cell lines in EWSR1-ETS-high versus -low condition

Project description:Cell lines have been essential for major discoveries in cancer including Ewing sarcoma (EwS). EwS is a highly aggressive pediatric bone or soft-tissue cancer characterized by oncogenic EWSR1-ETS fusion transcription factors converting polymorphic GGAA-microsatellites (mSats) into neo-enhancers. However, further detailed mechanistic evaluation of gene regulation in EwS have been hindered by the limited number of well-characterized cell line models. Here, we present the Ewing Sarcoma Cell Line Atlas (ESCLA) comprising 18 EwS cell lines with inducible EWSR1-ETS knockdown that were profiled by whole-genome-sequencing, DNA methylation arrays, gene expression and splicing arrays, mass spectrometry, and ChIP-seq for EWSR1-ETS and histone marks. Systematic analysis of these multi-dimensional data illuminated hundreds of new potential EWSR1-ETS target genes, the nature of EWSR1-ETS-preferred GGAA-mSats, and potential indirect modes of EWSR1-ETS-mediated gene regulation. Moreover, we identified putative co-regulatory transcription factors and heterogeneously regulated EWSR1-ETS target genes that may have implications for the clinical heterogeneity of EwS. Collectively, our freely available ESCLA constitutes an extremely rich resource for EwS research and highlights the power of leveraging multidimensional and comprehensive datasets to unravel principles of heterogeneous gene regulation by dominant fusion oncogenes.

2021-06-09 | GSE176190 | GEO

The Ewing Sarcoma Cell Line Atlas - Systematic analysis of genome-wide EWSR1-ETS binding and histone marks in 18 Ewing sarcoma cell lines by ChIP-seq

Project description:Cell lines have been essential for major discoveries in cancer including Ewing sarcoma (EwS). EwS is a highly aggressive pediatric bone or soft-tissue cancer characterized by oncogenic EWSR1-ETS fusion transcription factors converting polymorphic GGAA-microsatellites (mSats) into neo-enhancers. However, further detailed mechanistic evaluation of gene regulation in EwS have been hindered by the limited number of well-characterized cell line models. Here, we present the Ewing Sarcoma Cell Line Atlas (ESCLA) comprising 18 EwS cell lines with inducible EWSR1-ETS knockdown that were profiled by whole-genome-sequencing, DNA methylation arrays, gene expression and splicing arrays, mass spectrometry, and ChIP-seq for EWSR1-ETS and histone marks. Systematic analysis of these multi-dimensional data illuminated hundreds of new potential EWSR1-ETS target genes, the nature of EWSR1-ETS-preferred GGAA-mSats, and potential indirect modes of EWSR1-ETS-mediated gene regulation. Moreover, we identified putative co-regulatory transcription factors and heterogeneously regulated EWSR1-ETS target genes that may have implications for the clinical heterogeneity of EwS. Collectively, our freely available ESCLA constitutes an extremely rich resource for EwS research and highlights the power of leveraging multidimensional and comprehensive datasets to unravel principles of heterogeneous gene regulation by dominant fusion oncogenes.

2021-06-09 | GSE176400 | GEO

Pharmacologic Inhibition of Epigenetic Modification Reveals Targets of Aberrant Promoter Methylation in Ewing Sarcoma

Project description:Background: Ewing sarcoma, a highly aggressive tumor of children and young adults, is characterized most commonly by an 11;22 chromosomal translocation that fuses EWSR1 located at 22q12 with FLI1, coding for a member of the ETS family of transcription factors. Although genetic changes in Ewing sarcoma have been extensively researched, our understanding of the role of epigenetic modifications in this neoplasm is limited. Procedure: In an effort to improve our knowledge in the role of epigenetic changes in Ewing sarcoma we evaluated the in vitro antineoplastic effect of the DNA methyltransferase inhibitor 5-Aza-deoxycytidine (5-Aza-dC) and identified epigenetically silenced genes by pharmacologic unmasking of DNA methylation coupled with genome-wide expression profiling.

2014-03-05 | E-GEOD-44934 | biostudies-arrayexpress

Pharmacologic Inhibition of Epigenetic Modification Reveals Targets of Aberrant Promoter Methylation in Ewing Sarcoma

2014-03-05 | GSE44934 | GEO