A conditional mouse model of synovial sarcoma: insights into a myogenic origin

Cancer Cell. 2007 Apr;11(4):375-88. doi: 10.1016/j.ccr.2007.01.016.

Abstract

Synovial sarcoma is an aggressive soft-tissue malignancy marked by a unique t(X;18) translocation leading to expression of a chimeric SYT-SSX fusion protein. We report here a mouse model of synovial sarcoma based on conditional expression of the human SYT-SSX2. Using this model, we have identified myoblasts as a potential source of synovial sarcoma. Remarkably, within the skeletal muscle lineage, while expression of the oncoprotein in immature myoblasts leads to induction of synovial sarcoma with 100% penetrance, its expression in more differentiated cells induces myopathy without tumor induction. We also show that early widespread expression of the fusion protein disrupts normal embryogenesis, causing lethality.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Differentiation*
  • Disease Models, Animal*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Female
  • Gene Expression Profiling
  • Genes, Lethal
  • Humans
  • Immunoenzyme Techniques
  • In Situ Nick-End Labeling
  • Integrases / metabolism
  • Mice
  • Mice, Knockout
  • Microarray Analysis
  • Muscle, Skeletal / pathology*
  • Muscular Diseases / etiology*
  • Myoblasts, Skeletal / pathology*
  • Myogenic Regulatory Factor 5 / genetics
  • Myogenic Regulatory Factor 5 / metabolism
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoma, Synovial / genetics
  • Sarcoma, Synovial / metabolism
  • Sarcoma, Synovial / pathology*
  • Time Factors

Substances

  • Myf5 protein, mouse
  • Myogenic Regulatory Factor 5
  • Oncogene Proteins, Fusion
  • SYT-SSX fusion protein
  • Cre recombinase
  • Integrases

Associated data

  • GEO/GSE6461