Gordon, David J.Motwani, MonaPellman, David2016-06-142015Gordon, David J., Mona Motwani, and David Pellman. 2015. “Modeling the Initiation of Ewing Sarcoma Tumorigenesis in Differentiating Human Embryonic Stem Cells.” Oncogene :10.1038/onc.2015.368. doi:10.1038/onc.2015.368. http://dx.doi.org/10.1038/onc.2015.368.0950-9232http://nrs.harvard.edu/urn-3:HUL.InstRepos:27320208Oncogenic transformation in Ewing sarcoma tumors is driven by the fusion oncogene EWS-FLI1. However, despite the well-established role of EWS-FLI1 in tumor initiation, the development of models of Ewing sarcoma in human cells with defined genetic elements has been challenging. Here, we report a novel approach to model the initiation of Ewing sarcoma tumorigenesis that exploits the developmental and pluripotent potential of human embryonic stem cells. The inducible expression of EWS-FLI1 in embryoid bodies, or collections of differentiating stem cells, generates cells with properties of Ewing sarcoma tumors, including characteristics of transformation. These cell lines exhibit anchorage-independent growth, a lack of contact inhibition and a strong Ewing sarcoma gene expression signature. Furthermore, these cells also demonstrate a requirement for the persistent expression of EWS-FLI1 for cell survival and growth, which is a hallmark Ewing sarcoma tumors.en-USEwing sarcomaembryonic stem cellembryoid bodytransformationtumor initiationJournal Article2016-06-1410.1038/onc.2015.368