title: 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.affiliation: Department of Human Genetics, The Center for Children, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Malay
authors.initials: M
authors.lastname: Haldar
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Hancock
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Coffin
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Lessnick
authors.forename: Mario R
authors.initials: MR
authors.lastname: Capecchi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005804:Genes, Lethal; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019426:Integrases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D018482:Muscle, Skeletal / Q000473:pathology*; D009135:Muscular Diseases / Q000209:etiology*; D032448:Myoblasts, Skeletal / Q000473:pathology*; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
chemical_list: C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D015514:Oncogene Proteins, Fusion; C116512:SYT-SSX fusion protein; C045073:Cre recombinase; D019426:Integrases