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Patient\u2010derived xenograft (PDX) models are an important tool for cancer research, but their availability and utility remain limited in sarcoma. Here, we establish the SGH sarcoma PDX biobank, a living multi\u2010omics resource comprising 155 xenografts from 132 patients across 11 sarcoma histotypes, with osteosarcoma as the predominant subtype. This cohort is enriched for high\u2010risk sarcomas characterized by poor prognosis and widespread copy\u2010number alterations. Using this biobank, we show that extrachromosomal DNA (ecDNA) frequently drives high\u2010level oncogene amplification in osteosarcoma and that\n                    <jats:italic>MYC<\/jats:italic>\n                    ecDNA may underlie aggressive disease trajectories. Analyses of paired patient and PDX samples demonstrate that ecDNA is preferentially retained over intrachromosomal amplicons during engraftment and is stably maintained in PDX models. In addition, the PDX models largely recapitulate the histopathological and molecular features of their matched patient tumors while exhibiting distinct clonal evolutionary trajectories during engraftment. Finally, we identified potentially actionable genomic alterations within this PDX cohort, demonstrated genotype\u2010matched targeted therapy in a KRAS G12C\u2010mutant PDX model, and prioritized several candidate antibody\u2013drug conjugate targets. Together, this resource provides a platform for biological discovery and preclinical precision oncology for sarcoma.\n                  <\/jats:p>","DOI":"10.1002\/advs.78200","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:28:50Z","timestamp":1791865730000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Living Multi\u2010Omics PDX Biobank of High\u2010Risk Sarcomas Reveals ecDNA\u2010Driven Oncogene Amplification in Osteosarcoma and Enables Preclinical Precision Oncology"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5884-874X","authenticated-orcid":false,"given":"Weisong","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai People's Republic of China"},{"name":"Shanghai Bone Tumor Institution  Shanghai People's Republic of 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