Sarcoma RNAseq

Ewing sarcomas (ES) are aggressive bone and soft tissue cancers associated with aberrant activation of the EWS-FLI1 oncogene. Paradoxically, EWS-FLI1 does not induce ES in mice, thus the absence of a genetically defined model has hindered greater understanding of tumor pathogenesis. Here, we report PCG2, a novel mouse in which human GLI2A, an activator of Hedgehog (Hh) signaling, induces fast-growing, soft tissue tumors. Comprehensive analysis revealed remarkable similarity between PCG2 and ES at the pathology, immuno-phenotype, ultra-structure, and transcriptome levels. Moreover, we show that PCG2 tumors originate in bi-potent mesenchymal progenitors, providing insight into the elusive ES cellular origin. The striking PCG2 phenotype, which was strongly dependent on Gli1 dosage, suggests a greater role for oncogenic Hh signaling in ES etiology than previously recognized. Overall design: Six samples in total are included. Three TA muscle RNAs were sequenced and used for comparison with RNA from three primary tumors.