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

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.

• Authors: Malay Haldar, Jeffrey D Hancock, Cheryl M Coffin, Stephen L Lessnick, Mario R Capecchi
• Journal: Cancer cell (Cancer Cell) Vol. 11 Issue 4 Pg. 375-88 (Apr 2007) ISSN: 1535-6108 [Print] United States
• PMID: 17418413 (Publication Type: Journal Article)

Chemical References

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

Topics

• Animals
• Apoptosis
• Cell Differentiation
• Disease Models, Animal
• Embryo, Mammalian (cytology, 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, metabolism)
• Oncogene Proteins, Fusion (genetics, physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Sarcoma, Synovial (genetics, metabolism, pathology)
• Time Factors