PAX3-FOXO1 and FGFR4 in alveolar rhabdomyosarcoma

Mol Carcinog. 2012 Oct;51(10):807-15. doi: 10.1002/mc.20848. Epub 2011 Aug 31.


We and others have identified FGFR4 as a direct transcriptional target of the alveolar rhabdomyosarcoma (ARMS) specific fusion protein, PAX3-FOXO1. We hypothesized fibroblast growth factor receptor 4 (FGFR4) may act as an effector of PAX3-FOXO1, contributing to PAX3-FOXO1 tumorigenic phenotypes. However, we demonstrate that enhanced expression of FGFR4 does not contribute to inhibited differentiation, enhanced proliferation, or transformation downstream of PAX3-FOXO1 in primary mouse myoblasts. Therefore we were unable to identify any contribution of up regulation of wild type FGFR4 to PAX3-FOXO1 driven tumorigenesis. Conversely, a constitutively active mutant of FGFR4 can enhance primary myoblast proliferation and transformation, indicating activating mutations of FGFR4 could contribute to the development and progression of ARMS. We sequenced the FGFR4 mRNA from five ARMS cell lines and identified no somatic mutations, nor any association with any human single nucleotide polymorphism within the FGFR4 coding region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Gene Expression Regulation
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutation
  • Myoblasts / metabolism
  • Myoblasts / pathology
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism*
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism*
  • Polymorphism, Single Nucleotide
  • Receptor, Fibroblast Growth Factor, Type 4 / genetics*
  • Receptor, Fibroblast Growth Factor, Type 4 / metabolism
  • Rhabdomyosarcoma, Alveolar / genetics
  • Rhabdomyosarcoma, Alveolar / metabolism*
  • Rhabdomyosarcoma, Alveolar / pathology
  • Up-Regulation


  • Oncogene Proteins, Fusion
  • PAX3-FOXO1A fusion protein, human
  • Paired Box Transcription Factors
  • FGFR4 protein, human
  • Fgfr4 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 4

Associated data

  • GENBANK/JN007471
  • GENBANK/JN007472
  • GENBANK/JN007473
  • GENBANK/JN007474
  • GENBANK/JN007475
  • GENBANK/JN007476
  • GENBANK/JN007477
  • GENBANK/JN007478
  • GENBANK/JN007479
  • GENBANK/JN007480
  • GENBANK/JN007481
  • GENBANK/JN007482