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 the same 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 407 genes
Gene families ? Categorize these 407 genes by gene family
Show members (show 409 source identifiers mapped to 407 genes)
Version history 3.0: First introduced

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