title: Rhabdomyosarcomas utilize developmental, myogenic growth factors for disease advantage: a report from the Children's Oncology Group.
abstract: BACKGROUND
  Unresectable or metastatic disease represents the greatest obstacle to cure for children with rhabdomyosarcoma. In this study we sought to identify gene expression signatures of advanced stage and progressive disease.
  
  
  METHODS
  Using oligonucleotide gene expression analysis for a focused set of 60 genes, we analyzed the myogenic expression profiles of 89 rhabdomyosarcomas from the Intergroup Rhabdomyosarcoma Study-IV.
  
  
  RESULTS
  While the expression profile of rhabdomyosarcomas closely paralleled gene expression profiles of normal embryonic myogenic progenitors, growth factors were most closely associated with disease progression. Specifically, we identified platelet-derived growth factor (PDGF) receptors and insulin-like growth factor as strongly correlated with decreased failure-free survival. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) of an independent data set suggested that autocrine growth signaling, if present, is not regulated in a simple manner at the transcriptional level.
  
  
  CONCLUSIONS
  Increased transcriptional levels of PDGF receptors and insulin-like growth factor are associated with decreased survival in rhabdomyosarcomas. Dual blockade of these growth-factor-signaling pathways may be a valuable strategy in preclinical therapeutic studies.
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Utah, Salt Lake City, USA.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Blandford
authors.forename: Frederic G
authors.initials: FG
authors.lastname: Barr
authors.forename: James C
authors.initials: JC
authors.lastname: Lynch
authors.forename: R L
authors.initials: RL
authors.lastname: Randall
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Qualman
authors.forename: Charles
authors.initials: C
authors.lastname: Keller
mesh_terms: D000293:Adolescent; D000328:Adult; D019898:Autocrine Communication; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000378:metabolism* / Q000401:mortality; D013002:Somatomedins / Q000096:biosynthesis*; D014158:Transcription, Genetic
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D013002:Somatomedins; D017479:Receptors, Platelet-Derived Growth Factor