Distinct and overlapping sarcoma subtypes initiated from muscle stem and progenitor cells

Cell Rep. 2013 Nov 27;5(4):933-40. doi: 10.1016/j.celrep.2013.10.020. Epub 2013 Nov 14.


Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, whereas undifferentiated pleomorphic sarcoma (UPS) is one of the most common soft tissue sarcomas diagnosed in adults. To investigate the myogenic cell(s) of origin of these sarcomas, we used Pax7-CreER and MyoD-CreER mice to transform Pax7(+) and MyoD(+) myogenic progenitors by expressing oncogenic Kras(G12D) and deleting Trp53 in vivo. Pax7-CreER mice developed RMS and UPS, whereas MyoD-CreER mice developed UPS. Using gene set enrichment analysis, RMS and UPS each clustered specifically within their human counterparts. These results suggest that RMS and UPS have distinct and overlapping cells of origin within the muscle lineage. Taking them together, we have established mouse models of soft tissue sarcoma from muscle stem and progenitor cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation, Neoplastic / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle Development / genetics
  • MyoD Protein / genetics*
  • Myoblasts, Skeletal / pathology*
  • Neoplastic Stem Cells / enzymology
  • Neoplastic Stem Cells / pathology*
  • PAX7 Transcription Factor / genetics*
  • Proto-Oncogene Proteins p21(ras) / biosynthesis
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Rhabdomyosarcoma / genetics
  • Rhabdomyosarcoma / pathology*
  • Tumor Suppressor Protein p53 / genetics


  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • PAX7 Transcription Factor
  • Pax7 protein, mouse
  • Tumor Suppressor Protein p53
  • Hras protein, mouse
  • Proto-Oncogene Proteins p21(ras)

Associated data

  • GEO/GSE46836