Gene Set: ZHANG_TARGETS_OF_EWSR1_FLI1_FUSION

Standard name ZHANG_TARGETS_OF_EWSR1_FLI1_FUSION
Systematic name M18322
Brief description Genes up-regulated in RD-EF cells (rhabdomyosarcoma) engineered to express EWSR1-FLI1 fusion [GeneID=2130;2313] and which are also highly expressed in Ewing's famliy tumors.
Full description or abstract Tumor-specific translocations are common in tumors of mesenchymal origin. Whether the translocation determines the phenotype, or vice versa, is debatable. Ewing's family tumors (EFT) are consistently associated with an EWS-FLI1 translocation and a primitive neural phenotype. Histogenesis and classification are therefore uncertain. To test whether EWS-FLI1 fusion gene expression is responsible for the primitive neuroectodermal phenotype of EFT, we established a tetracycline-inducible EWS-FLI1 expression system in a rhabdomyosarcoma cell line RD. Cell morphology changed after EWS-FLI1 expression, resembling cultured EFT cells. Xenografts showed typical EFT features, distinct from tumors formed by parental RD. Neuron-specific microtubule gene MAPT, parasympathetic marker cholecystokinin, and epithelial marker keratin 18 were up-regulated. Conversely, myogenesis was diminished. Comparison of the up-regulated genes in RD-EF with the Ewing's signature genes identified important EWS-FLI1 downstream genes, many involved in neural crest differentiation. These results were validated by real-time reverse transcription-PCR analysis and RNA interference technology using small interfering RNA against EWS-FLI1 breakpoint. The present study shows that the neural phenotype of Ewing's tumors is attributable to the EWS-FLI1 expression and the resultant phenotype resembles developing neural crest. Such tumors have a limited neural phenotype regardless of tissue of origin. These findings challenge traditional views of histogenesis and tumor origin.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 15930281   Authors: Hu-Lieskovan S,Zhang J,Wu L,Shimada H,Schofield DE,Triche TJ
Exact source Table 1
Related gene sets (show 112 gene sets from the same authors)
External links  
Filtered by similarity
Organism Homo sapiens
Contributed by Kevin Vogelsang (MSigDB Team)
Source platform AFFY_HG_U95
Dataset references  
Download gene set format: grp | text | gmt | gmx | xml
Compute overlaps (show collections to investigate for overlap with this gene set)
Compendia expression profiles GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 87 genes
Gene families Categorize these 87 genes by gene family
Show members (show 107 members mapped to 87 genes)
Version history 3.0: Renamed from ZHANG_EFT_EWSFLI1_UP

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