Distinct and Overlapping Sarcoma Subtypes Initiated from Muscle Stem and Progenitor Cells
oleh: Jordan M. Blum, Leonor Añó, Zhizhong Li, David Van Mater, Brian D. Bennett, Mohit Sachdeva, Irina Lagutina, Minsi Zhang, Jeffrey K. Mito, Leslie G. Dodd, Diana M. Cardona, Rebecca D. Dodd, Nerissa Williams, Yan Ma, Christoph Lepper, Corinne M. Linardic, Sayan Mukherjee, Gerard C. Grosveld, Chen-Ming Fan, David G. Kirsch
| Format: | Article |
|---|---|
| Diterbitkan: | Elsevier 2013-11-01 |
Deskripsi
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, whereas undifferentiated pleomorphic sarcoma (UPS) is one of the most common soft tissue sarcomas diagnosed in adults. To investigate the myogenic cell(s) of origin of these sarcomas, we used Pax7-CreER and MyoD-CreER mice to transform Pax7+ and MyoD+ myogenic progenitors by expressing oncogenic KrasG12D and deleting Trp53 in vivo. Pax7-CreER mice developed RMS and UPS, whereas MyoD-CreER mice developed UPS. Using gene set enrichment analysis, RMS and UPS each clustered specifically within their human counterparts. These results suggest that RMS and UPS have distinct and overlapping cells of origin within the muscle lineage. Taking them together, we have established mouse models of soft tissue sarcoma from muscle stem and progenitor cells.