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.
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