To establish an optimized protocol for orthotopic induction of murine STS by EPO, we chose a vector combination conveying overexpression of oncogenic RAS and inactivation of Trp53, which have been shown to co-occur in several high-risk sarcoma entities, such as embryonal RMS (eRMS) and have previously been validated to efficiently drive sarcoma in mice from the Rosa26 locus upon Cre-LoxP recombination14. Here, TP53 is linked to sarcoma.