Human Gene Set: REN_ALVEOLAR_RHABDOMYOSARCOMA_DN


Standard name REN_ALVEOLAR_RHABDOMYOSARCOMA_DN
Systematic name M19541
Brief description Genes commonly down-regulated in human alveolar rhabdomyosarcoma (ARMS) and its mouse model overexpressing PAX3-FOXO1 [GeneID=5077;2308] fusion.
Full description or abstract Alveolar rhabdomyosarcomas (ARMS) are highly malignant soft-tissue sarcomas that arise in children, adolescents, and young adults. Although formation and expression of the PAX-FKHR fusion genes is thought to be the initiating event in this cancer, the role of PAX-FKHR in the neoplastic process remains largely unknown in a progenitor cell that is undefined. We hypothesize that PAX-FKHR determine the ARMS progenitor to the skeletal muscle lineage, which when coupled to the inactivation and/or activation of critical cell signaling pathways leads to the formation of ARMS. Because a number of studies have proposed that mesenchymal stem cells (MSC) are the progenitor for several of the sarcomas, we tested this hypothesis in MSCs. We show that PAX-FKHR induce skeletal myogenesis in MSCs by transactivating MyoD and myogenin. Despite exhibiting enhanced growth in vitro, the PAX-FKHR-expressing populations do not form colonies in soft agar or tumors in mice. Expression of dominant-negative p53, or the SV40 early region, elicits tumor formation in some of the PAX-FKHR-expressing populations. Additional activation of the Ras signaling pathway leads to highly malignant tumor formation for all of the populations. The PAX-FKHR-expressing tumors were shown to have histologic, immunohistochemical, and gene expression profiles similar to human ARMS. Our results show the critical role played by PAX-FKHR in determining the molecular, myogenic, and histologic phenotype of ARMS. More importantly, we identify MSCs as a progenitor that can give rise to ARMS.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18701482   Authors: Ren YX,Finckenstein FG,Abdueva DA,Shahbazian V,Chung B,Weinberg KI,Triche TJ,Shimada H,Anderson MJ
Exact source Table 12S
Related gene sets (show 1 additional gene sets from the source publication)

(show 13 gene sets from any of these authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform or
identifier namespace		 AFFY_HG_U133
Dataset references (show 6 datasets)
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 404 genes
Gene families ? Categorize these 404 genes by gene family
Show members (show 409 source identifiers mapped to 404 genes)
Version history 3.0: First introduced


Creative Commons Attribution 4.0 International License (CC-BY-4.0)

The contents of this gene set are protected by copyright (c) 2004-2026 Broad Institute, Inc., Massachusetts Institute of Technology, and Regents of the University of California, subject to the terms and conditions of the Creative Commons Attribution 4.0 International License.

See the full MSigDB license terms here.