All aggressive RMS xenografted PDSOs retained the PAX3::FOXO1 fusion gene, as well as other genetic alterations associated with aggressive features like TP53 mutations, FGFR4 mutations, PIK3CA or NRAS mutations, and alterations in cell cycle-related genes.Fifteen Ewing sarcoma xenografted PDSOs were established, with 13 of them showing the EWSR1::FLI1 translocation, and one each showing FUS::ERG and EWSR1::FEV translocations. The xenografted PDSOs also exhibited other genetic alterations such as TP53 mutations, STAG2 mutations or deletions, and CDKN2A deletions. Here, STAG2 is linked to Ewing sarcoma.