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Synovial sarcoma: from genetics to genetic-based animal modeling Haldar M; Randall RL; Capecchi MRClin Orthop Relat Res 2008[Sep]; 466 (9): 2156-67Synovial sarcomas are highly aggressive mesenchymal cancers that show modest response to conventional cytotoxic chemotherapy, suggesting a definite need for improved biotargeted agents. Progress has been hampered by the lack of insight into pathogenesis of this deadly disease. The presence of a specific diagnostic t(X;18) translocation leading to expression of the unique SYT-SSX fusion protein in effectively all cases of synovial sarcoma suggests a role in the etiology. Other nonspecific anomalies such as overexpression of Bcl-2, HER-2/neu, and EGFR have been reported, but their role in the pathogenesis remains unclear. Using gene targeting, we recently generated mice conditionally expressing the human SYT-SSX2 fusion gene from mouse endogenous ROSA26 promoter in chosen tissue types in the presence of Cre recombinase. These mice develop synovial sarcoma when SYT-SSX2 is expressed within myoblasts, thereby identifying a source of this enigmatic tumor and establishing a mouse model of this disease that recapitulates the clinical, histologic, immunohistochemical, and transcriptional profile of human synovial sarcomas. We review the genetics of synovial sarcoma and discuss the usefulness of genetics-based mouse models as a valuable research tool in the hunt for key molecular determinants of this lethal disease as well as a preclinical platform for designing and evaluating novel treatment strategies.|*Disease Models, Animal[MESH]|Animals[MESH]|Cadherins/metabolism[MESH]|Humans[MESH]|Mice[MESH]|Myoblasts/metabolism[MESH]|Neoplasm Proteins/*genetics[MESH]|Oligonucleotide Array Sequence Analysis[MESH]|Proto-Oncogene Proteins/*genetics[MESH]|Repressor Proteins/*genetics[MESH]|Sarcoma, Synovial/*genetics[MESH]|Translocation, Genetic/physiology[MESH]|Xenograft Model Antitumor Assays[MESH] |
