Ewing sarcoma - WGS - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001001051 | EGA |
REPOSITORIES: EGA
Publications
Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations.
Tirode Franck F Surdez Didier D Ma Xiaotu X Parker Matthew M Le Deley Marie Cécile MC Bahrami Armita A Zhang Zhaojie Z Lapouble Eve E Grossetête-Lalami Sandrine S Rusch Michael M Reynaud Stéphanie S Rio-Frio Thomas T Hedlund Erin E Wu Gang G Chen Xiang X Pierron Gaelle G Oberlin Odile O Zaidi Sakina S Lemmon Gordon G Gupta Pankaj P Vadodaria Bhavin B Easton John J Gut Marta M Ding Li L Mardis Elaine R ER Wilson Richard K RK Shurtleff Sheila S Laurence Valérie V Michon Jean J Marec-Bérard Perrine P Gut Ivo I Downing James J Dyer Michael M Zhang Jinghui J Delattre Olivier O
Cancer discovery 20140915 11
<h4>Unlabelled</h4>Ewing sarcoma is a primary bone tumor initiated by EWSR1-ETS gene fusions. To identify secondary genetic lesions that contribute to tumor progression, we performed whole-genome sequencing of 112 Ewing sarcoma samples and matched germline DNA. Overall, Ewing sarcoma tumors had relatively few single-nucleotide variants, indels, structural variants, and copy-number alterations. Apart from whole chromosome arm copy-number changes, the most common somatic mutations were detected in ...[more]
Similar Datasets
Project description:Description not provided
| EGAD00001004493 | EGA
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.
2012-02-11 | GSE34620 | GEO
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). STAG2 loss-of-function mutation is the most frequent secondary genetic alteration in Ewing sarcoma, an aggressive bone tumor driven by the chimeric EWSR1-FLI1 transcription factor. STAG2 encodes an integral member of the cohesin complex, a ring-shaped multi-protein structure, which is essential to shape the architecture and expression of the genome with CTCF. Combining this cohort with our previously published series (GSE34620), we show that a signature of commonly downregulated genes upon STAG2 mutation in A673 and TC71 and linked to at least one EWSR1-FLI1 bound GGAA microsatellite enhancer chain element inferred form H3K27ac HiChIP predict poor overall survival in Ewing sarcoma patients.
2021-04-29 | GSE142162 | GEO
Project description: Not available
| S-EPMC11195538 | biostudies-literature
Project description:Ewing’s Sarcoma (ES) is characterized by specific chromosomal translocations, the most common being t(11;22)(q24;q12). Additionally, other types of genetic abnormalities may occur and be relevant to explain the variable tumoural biology and clinical outcome. We have carried out a high-resolution array CGH and expression profiling on 25 ES tumour samples to characterize the DNA copy number aberrations (CNA) occurring in these tumours and to determine their association with gene expression profiles (GEO Series accession number: GSE8303) and their clinical outcome. CNA were observed in 84% of the cases. We observed a median number of 3 aberrations per case. Besides numerical chromosomal changes, smaller aberrations were found and defined at chromosomes 5p, 7q and 9p. All CNA were compiled to define the smallest overlapping regions of imbalance (SORI). Thirty five SORI were delimited. Bioinformatic analyses were conducted to identify subgroups according to the pattern of genomic instability obtained. Unsupervised and supervised clustering analyses (using SORI as variables) segregated the tumours into two distinct groups: one genomically stable (≤ 3 CNA) and another genomically unstable one (> 3 CNA). The genomic unstable group showed a statistically significant shorter overall survival and was more refractory to chemotherapy. This report elucidates data about genomic instability in ES, based on CNA and expression profiling for the first time, and shows that a genomically unstable group of Ewing tumours is correlated with a significant poor prognosis. Keywords: Comparative Genomic Hybridization - array; Genomic Instability
2007-11-09 | GSE8398 | GEO
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
Project description:Ewing Sarcoma (EwS) is a rare pediatric malignancy characterized by a unique t(11:22) (q24;q12) translocation resulting in the EWSR1::FLI1 fusion. Recent reports indicate the EWSR1::FLI1 fusion onco-protein drives aberrant expression of numerous transcripts, including Lipoxygenase Homology Domains 1 (LOX¬HD1). Given its highly restricted protein expression pattern and role in EwS tumorigenesis and metastasis, LOXHD1 may serve as a novel immunotherapeutic target in this malignancy. LOXHD1 immunogenic epitopes restricted to HLA-A*02:01 allowed for the isolation of high avidity TCRs. LOXHD1-specific TCR engineered CD8+ T cells confer cytotoxic activity against a panel of HLA-A*02:01+ EwS tumor cell lines and adoptive transfer leads to tumor eradication in a mouse xenograft model of EwS. This study nominates LOXHD1 as an onco-fusion regulated / non-mutated EwS tumor associated antigen with expression limited to inner hair cells of the cochlea, adult testis, and EwS
2025-05-06 | PXD046803 | Pride
Project description: Not available
| S-EPMC7607515 | biostudies-literature
Project description:We show that EWS-FLI1, an aberrant transcription factor responsible for the pathogenesis of Ewing sarcoma, reprograms gene regulatory circuits by directly inducing or directly repressing enhancers. At GGAA repeats, which lack regulatory potential in other cell types and are not evolutionarily conserved, EWS- FLI1 multimers potently induce chromatin opening, recruit p300 and WDR5, and create de novo enhancers. GGAA repeat enhancers can loop to physically interact with target promoters, as demonstrated by chromosome conformation capture assays. Conversely, EWS-FLI1 inactivates conserved enhancers containing canonical ETS motifs by displacing wild-type ETS transcription factors and abrogating p300 recruitment. Mesenchymal stem cells (MSCs) and a Ewing sarcoma cell line (SKNMC) were analyzed by ATAC-seq. EWS-FLI1 was expressed in MSCs using a lentiviral vector (pLIV EWSFLI1 or pLIV empty vector control). * Raw data not provided for the MSC samples. *
2014-10-30 | E-GEOD-61951 | biostudies-arrayexpress
Project description:We show that EWS-FLI1, an aberrant transcription factor responsible for the pathogenesis of Ewing sarcoma, reprograms gene regulatory circuits by directly inducing or directly repressing enhancers. At GGAA repeats, which lack regulatory potential in other cell types and are not evolutionarily conserved, EWS- FLI1 multimers potently induce chromatin opening, recruit p300 and WDR5, and create de novo enhancers. GGAA repeat enhancers can loop to physically interact with target promoters, as demonstrated by chromosome conformation capture assays. Conversely, EWS-FLI1 inactivates conserved enhancers containing canonical ETS motifs by displacing wild-type ETS transcription factors and abrogating p300 recruitment. ChIP-seq for of 4 histone modifications (H3K27ac, H3K4me1, H3K4me3 and H3K27me3), FLI1, p300, WDR5, ELF1 and GABPA in primary Ewing sarcomas, Ewing sarcoma cell lines (A673 and SKMNC cells), and mesenchymal stem cells (MSC). EWS-FLI1 was knocked down in Ewing sarcoma cell lines with lentiviral shRNAs (shFLI1 and shGFP control). EWS-FLI1 was expressed in MSCs with lentiviral expression vectors (pLIV EWSFLI1 or pLIV empty vector control). * Raw data not provided for the MSC and Primary Ewing sarcoma samples. *
2014-10-30 | E-GEOD-61944 | biostudies-arrayexpress