Rhabdomyosarcomas utilize developmental, myogenic growth factors for disease advantage: A report from the children's oncology group

Mary C. Blandford, Frederic G. Barr, James C. Lynch, R Randall, Stephen J. Qualman, Charles Keller

Research output: Contribution to journalArticle

42 Scopus citations

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. Procedure. Using oligonucleotide gene expression analysis for a focused set of 60 genes, we analyzed the myogenic expression profiles of 89 rhabdomyosarcomas from the Intergroup Rhab-domyosarcoma 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.

Original languageEnglish (US)
Pages (from-to)329-338
Number of pages10
JournalPediatric Blood and Cancer
Volume46
Issue number3
DOIs
StatePublished - Mar 1 2006
Externally publishedYes

Keywords

  • Insulin-like growth factor
  • Metastasis
  • Myogenesis
  • Platelet-derived growth factor
  • Progression
  • Rhabdomyosarcoma

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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