Human Gene Set: KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN


Standard name KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN
Systematic name M13206
Brief description Genes down-regulated in TC71 and EWS502 cells (Ewing's sarcoma) by EWSR1-FLI1 [GeneID=2130;2314] as inferred from RNAi knockdown of this fusion protein.
Full description or abstract A number of solid tumors, such as alveolar rhabdomyosarcoma, synovial sarcoma, and myxoid liposarcoma, are associated with recurrent translocation events that encode fusion proteins. Ewing's sarcoma is a pediatric tumor that serves as a prototype for this tumor class. Ewing's sarcomas usually harbor the (11;22)(q24;q12) translocation. The t(11;22) encodes the EWS/FLI fusion oncoprotein. EWS/FLI functions as an aberrant transcription factor, but the key target genes that are involved in oncogenesis are largely unknown. Although some target genes have been defined, many of these have been identified in heterologous model systems with uncertain relevance to the human disease. To understand the function of EWS/FLI and its targets in a more clinically relevant system, we used retroviral-mediated RNAi to knock-down the fusion protein in patient-derived Ewing's sarcoma cell lines. By combining transcriptional profiling data from three of these lines, we identified a conserved transcriptional response to EWS/FLI. The gene that was most reproducibly up-regulated by EWS/FLI was NR0B1. NR0B1 is a developmentally important orphan nuclear receptor with no previously defined role in oncogenesis. We validated NR0B1 as an EWS/FLI-dysregulated gene and confirmed its expression in primary human tumor samples. Functional studies revealed that ongoing NR0B1 expression is required for the transformed phenotype of Ewing's sarcoma. These studies define a new role for NR0B1 in oncogenic transformation and emphasize the utility of analyzing the function of EWS/FLI in Ewing's sarcoma cells.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17114343   Authors: Kinsey M,Smith R,Lessnick SL
Exact source Suppl. Data 2: 436 EWSFLI downregulated genes
Related gene sets (show 1 additional gene sets from the source publication)

(show 9 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
Source platform or
identifier namespace		 AFFY_HG_U133
Dataset references  
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 337 genes
Gene families ? Categorize these 337 genes by gene family
Show members (show 436 source identifiers mapped to 337 genes)
Version history 3.0: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.