A conditional mouse model of synovial sarcoma: insights into a myogenic origin.
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.
Pubmed ID: 17418413 RIS Download
Animals | Apoptosis | Cell Differentiation | Disease Models, Animal | Embryo, Mammalian | Female | Gene Expression Profiling | Genes, Lethal | Humans | Immunoenzyme Techniques | In Situ Nick-End Labeling | Integrases | Mice | Mice, Knockout | Microarray Analysis | Muscle, Skeletal | Muscular Diseases | Myoblasts, Skeletal | Myogenic Regulatory Factor 5 | Oncogene Proteins, Fusion | Reverse Transcriptase Polymerase Chain Reaction | Sarcoma, Synovial | Time Factors