Human Gene Set: TORCHIA_TARGETS_OF_EWSR1_FLI1_FUSION_TOP20_DN

For the Mouse gene set with the same name, see TORCHIA_TARGETS_OF_EWSR1_FLI1_FUSION_TOP20_DN

Standard name TORCHIA_TARGETS_OF_EWSR1_FLI1_FUSION_TOP20_DN
Systematic name M2347
Brief description Top 20 down-regulated genes in leukemic progenitor cells expressing activated fusion of ESWR1 and FLI1 [GeneID=2130] [GeneID=2313] compared to normal hematopoetic progenitors.
Full description or abstract EWS/FLI-1 is a chimeric oncogene generated by chromosomal translocation in Ewing tumors, a family of poorly differentiated pediatric tumors arising predominantly in bone but also in soft tissue. The fusion gene combines sequences encoding a strong transactivating domain from the EWS protein with the DNA binding domain of FLI-1, an ETS transcription factor. A related fusion, TLS/ERG, has been found in myeloid leukemia. To determine EWS/FLI-1 function in vivo, we engineered mice with Cre-inducible expression of EWS/FLI-1 from the ubiquitous Rosa26 locus. When crossed with Mx1-cre mice, Cre-mediated activation of EWS/FLI-1 resulted in the rapid development of myeloid/erythroid leukemia characterized by expansion of primitive mononuclear cells causing hepatomegaly, splenomegaly, severe anemia, and death. The disease could be transplanted serially into naïve recipients. Gene expression profiles of primary and transplanted animals were highly similar, suggesting that activation of EWS/FLI-1 was the primary event leading to disease in this model. The Cre-inducible EWS/FLI-1 mouse provides a novel model system to study the contribution of this oncogene to malignant disease in vivo.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17875932   Authors: Torchia EC,Boyd K,Rehg JE,Qu C,Baker SJ
Exact source Table 5: Ratio < 0
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(show 15 gene sets from the same authors)
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Source species Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
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AFFY_Mouse430
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Version history 3.1: First introduced

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