A CreER-based random induction strategy for modeling translocation-associated sarcomas in mice.
Previously, we reported modeling synovial sarcomas in mice by conditionally expressing the human t(X;18) translocation-derived SYT-SSX2 fusion protein in Myf5-expressing myoblasts. Using a tamoxifen-inducible CreER system in mice, we show here that sporadic expression of SYT-SSX2 across multiple tissue types leads to exclusive formation of synovial sarcoma-like tumors, whereas its widespread expression is lethal. Certain clinical and histologic features of tumors in this new model suggest additional nonmyoblast origin for synovial sarcoma. CreER-based sporadic expression both avoids the severe early developmental phenotypes associated with widespread SYT-SSX2 expression and better models natural pathogenesis of cancers in which transformed cells usually arise within an environment of largely normal cells. Furthermore, this strategy may recapitulate multiple potential cellular origins within a single model system.
Haldar
Malay
M
Department of Human Genetics, University of Utah, School of Medicine, Salt Lake City, Utah 84112, USA.
Hedberg
Matthew L
ML
Hockin
Matthew F
MF
Capecchi
Mario R
MR
D000818:Animals; D019426:Integrases / Q000235:genetics*; D051379:Mice; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics; D013584:Sarcoma, Synovial / Q000235:genetics* / Q000473:pathology*; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000473:pathology*; D014178:Translocation, Genetic
D015514:Oncogene Proteins, Fusion; C116512:SYT-SSX fusion protein; C045073:Cre recombinase; D019426:Integrases