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
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Animals
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Apoptosis
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Cell Differentiation*
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Disease Models, Animal*
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Embryo, Mammalian / cytology
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Embryo, Mammalian / metabolism
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Female
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Gene Expression Profiling
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Genes, Lethal
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Humans
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Immunoenzyme Techniques
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In Situ Nick-End Labeling
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Integrases / metabolism
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Mice
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Mice, Knockout
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Microarray Analysis
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Muscle, Skeletal / pathology*
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Muscular Diseases / etiology*
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Myoblasts, Skeletal / pathology*
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Myogenic Regulatory Factor 5 / genetics
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Myogenic Regulatory Factor 5 / metabolism
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / physiology
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Reverse Transcriptase Polymerase Chain Reaction
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Sarcoma, Synovial / genetics
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Sarcoma, Synovial / metabolism
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Sarcoma, Synovial / pathology*
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Time Factors
Substances
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Myf5 protein, mouse
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Myogenic Regulatory Factor 5
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Oncogene Proteins, Fusion
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SYT-SSX fusion protein
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Cre recombinase
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Integrases