Distinct and Overlapping Sarcoma Subtypes Initiated from Muscle Stem and Progenitor Cells
- Blum, Jordan M.
- Añó, Leonor
- Li, Zhizhong
- VanMater, David
- Bennett, Brian D.
- Sachdeva, Mohit
- Lagutina, Irina
- Zhang, Minsi
- Mito, Jeffrey K.
- Dodd, Leslie G.
- Cardona, Diana M.
- Dodd, Rebecca D.
- Williams, Nerissa
- Ma, Yan
- Lepper, Christoph
- Linardic, Corinne M.
- Mukherjee, Sayan
- Grosveld, Gerard C.
- Fan, Chen Ming
- Kirsch, David G.
DOIAbstract
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, while 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 p53 in vivo. Pax7-CreER mice developed RMS and UPS, while 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. Taken together, we have established novel mouse ...
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