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Identification of a novel FUS/ETV4 fusion and comparative analysis with other Ewing sarcoma fusion proteins

ABSTRACT: Identification of a novel FUS/ETV4 fusion and comparative analysis with other Ewing sarcoma fusion proteins

PROVIDER: PRJNA724650 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14309529_1.fastq.gz	Fastqsanger.gz
	SRR14309529_2.fastq.gz	Fastqsanger.gz
	SRR14309530_1.fastq.gz	Fastqsanger.gz
	SRR14309530_2.fastq.gz	Fastqsanger.gz
	SRR14309531_1.fastq.gz	Fastqsanger.gz

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Identification of a novel FUS/ETV4 fusion and comparative analysis with other Ewing sarcoma fusion proteins [CUT&Tag]

Project description:Identification of a novel FUS/ETV4 fusion and comparative analysis with other Ewing sarcoma fusion proteins [CUT&Tag]

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Identification of a novel FUS/ETV4 fusion and comparative analysis with other Ewing sarcoma fusion proteins [RNA-seq]

Project description:Identification of a novel FUS/ETV4 fusion and comparative analysis with other Ewing sarcoma fusion proteins [RNA-seq]

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Identification of a novel FUS/ETV4 fusion and comparative analysis with other Ewing sarcoma fusion proteins [RNA-seq]

Project description:The purpose of this study was to determine the transcriptional regulatory similarities and differences in the FET/ETS translocations that have been identified as drivers of Ewing sarcoma.

2021-09-15 | GSE173183 | GEO

Identification of a novel FUS/ETV4 fusion and comparative analysis with other Ewing sarcoma fusion proteins [CUT&Tag]

Project description:The purpose of this study was to determine the genomic localization similarities and differences in the FET/ETS translocations that have been identified as drivers of Ewing sarcoma.

2021-09-15 | GSE173184 | GEO

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

Identification of a Novel FUS/ETV4 Fusion and Comparative Analysis with Other Ewing Sarcoma Fusion Proteins.

Project description:Ewing sarcoma is a pediatric bone cancer defined by a chromosomal translocation fusing one of the FET family members to an ETS transcription factor. There have been seven reported chromosomal translocations, with the most recent reported over a decade ago. We now report a novel FET/ETS translocation involving FUS and ETV4 detected in a patient with Ewing sarcoma. Here, we characterized FUS/ETV4 by performing genomic localization and transcriptional regulatory studies on numerous FET/ETS fusions in a Ewing sarcoma cellular model. Through this comparative analysis, we demonstrate significant similarities across these fusions, and in doing so, validate FUS/ETV4 as a bona fide Ewing sarcoma translocation. This study presents the first genomic comparison of Ewing sarcoma-associated translocations and reveals that the FET/ETS fusions share highly similar, but not identical, genomic localization and transcriptional regulation patterns. These data strengthen the notion that FET/ETS fusions are key drivers of, and thus pathognomonic for, Ewing sarcoma. IMPLICATIONS: Identification and initial characterization of the novel Ewing sarcoma fusion, FUS/ETV4, expands the family of Ewing fusions and extends the diagnostic possibilities for this aggressive tumor of adolescents and young adults.

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RUNX3 Facilitates Growth of Ewing Sarcoma Cells

Project description:Ewing sarcoma is an aggressive pediatric small round cell tumor that predominantly occurs in bone. Approximately 85% of Ewing sarcomas harbor the EWS/FLI fusion protein, which arises from a chromosomal translocation, t(11:22)(q24:q12). EWS/FLI interacts with numerous lineage-essential transcription factors to maintain mesenchymal progenitors in an undifferentiated state. We previously showed that EWS/FLI binds the osteogenic transcription factor RUNX2 and prevents osteoblast differentiation. In this study, we investigated the role of another Runt-domain protein, RUNX3, in Ewing sarcoma. RUNX3 participates in mesenchymal-derived bone formation and is a context dependent tumor suppressor and oncogene. RUNX3 was detected in all Ewing sarcoma cells examined, whereas RUNX2 was detected in only 73% of specimens. Like RUNX2, RUNX3 binds to EWS/FLI via its Runt domain. EWS/FLI prevented RUNX3 from activating the transcription of a RUNX-responsive reporter, p6OSE2. Stable suppression of RUNX3 expression in the Ewing sarcoma cell line A673 delayed colony growth in anchorage independent soft agar assays and reversed expression of EWS/FLI-responsive genes. These results demonstrate an important role for RUNX3 in Ewing sarcoma. RNA-seq to compare transcriptiome of control A673 ewing sarcoma cells stably expression a non-target or RUNX3 shRNA

2014-05-01 | E-GEOD-56900 | biostudies-arrayexpress

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

FET fusion oncoprotein-regulated genes in HT1080 cell line

Project description:Some specific sarcomas and leukemias are defined by characteristic FET (FUS, EWSR1, TAF15) fusion oncogenes. Myxoid liposarcoma and Ewing sarcoma are the most common entities characterized by FUS-DDIT3 and EWSR1-FLI1, respectively. Here, we performed whole transcriptome analysis of HT1080 cells with either ectopic FUS-DDIT3 or ectopic EWSR1-FLI1 expression.

2019-03-12 | GSE125941 | GEO

Identification of FET-oncoprotein-interacting proteins by immunoprecipitation and mass spectrometry analysis in sarcoma cell lines

Project description:The FET family of fusion oncogenes carry one of the three genes, FUS, EWSR1 or TAF15, as 5’‑partners juxtaposed to one of many different DNA binding transcription factor genes as 3’‑partners. FET fusion oncogenes are pathognomonic for many types of sarcoma and leukemia, such as FUS-DDIT3 in myxoid liposarcoma (MLS) and EWSR1-FLI1 in Ewing sarcoma (EWS). We used recombinant FET N-terminal domains in a pulldown screen to find interaction partners to the FET proteins and identified components of the SWI/SNF complex. The ~2 MDa SWI/SNF chromatin remodeling complex utilizes energy from ATP hydrolysis to remodel nucleosomes and expose DNA. We used immunoprecipitation followed by mass spectrometry or western blot analysis to extensively characterize the interaction between FET fusion oncoproteins and the SWI/SNF complex.

2019-03-13 | PXD012680 | Pride

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