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Most EwS develop in bone, while it originates from connective, adipose, or muscle tissue less frequently. We report the establishment of new human EwS cell lines, all of which carry a t(11;22)(q24;q12) translocation generating the oncogenic transcription factor EWSR1::FLI1. Sequencing of the chimeric mRNAs indicated genomic DNA breakpoints localized in intron 8 of the\n                    <jats:italic>EWSR1<\/jats:italic>\n                    gene and three different introns of the translocation partner gene\n                    <jats:italic>FLI1<\/jats:italic>\n                    . While three EwS cell lines carry the\n                    <jats:italic>EWSR1::FLI1<\/jats:italic>\n                    fusions of ex7\/ex6 (type I) or ex7\/ex5 (type II), the\n                    <jats:italic>EWSR1::FLI1<\/jats:italic>\n                    fusion variant ex7\/ex7 (type IV) is described for the first time in a continuous EwS model. The cell lines presented genomic, epigenomic, and transcriptomic stability over a period of 6 months, though some variations in the chromosomal aberrations were observed in one cell line.\n                    <jats:italic>TP53<\/jats:italic>\n                    ,\n                    <jats:italic>STAG2<\/jats:italic>\n                    , and\n                    <jats:italic>CDKN2A\/B<\/jats:italic>\n                    mutations were the most frequent and most relevant mutations in our cell line panel. The\n                    <jats:italic>TP53<\/jats:italic>\n                    mutational status seemed to have the biggest impact on drug sensitivity profiles. The new EwS models presented here may help to identify small molecule inhibitors that act directly on\n                    <jats:italic>EWSR1::FLI1<\/jats:italic>\n                    fusion proteins or uncover other genetic vulnerabilities of the altered epigenome and transcriptome in EwS, which would contribute to a better understanding of Ewing sarcoma tumorigenesis.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70172","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T13:36:06Z","timestamp":1758893766000},"page":"642-655","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["New cell lines expanding the diversity of Ewing sarcoma models"],"prefix":"10.1002","volume":"158","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4458-1609","authenticated-orcid":false,"given":"Maximilian","family":"Kerkhoff","sequence":"first","affiliation":[{"name":"Pediatrics III, West German Cancer 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Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawid","family":"Krzeciesa","sequence":"additional","affiliation":[{"name":"German Cancer Consortium (DKTK) Site Essen Cancer Research Center (NCT) Cologne\u2010  Essen Germany"},{"name":"Faculty of Medicine University of Duisburg\u2010Essen  Essen Germany"},{"name":"Department of Medical Oncology, Sarcoma Center, West German Cancer Center University Duisburg\u2010Essen, Medical School  Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian","family":"Bretschneider","sequence":"additional","affiliation":[{"name":"Pediatrics III, West German Cancer Center University Hospital Essen  Essen Germany"},{"name":"German Cancer Consortium (DKTK) Site Essen Cancer Research Center (NCT) Cologne\u2010  Essen Germany"},{"name":"Faculty of Medicine University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauline R.","family":"Plaumann","sequence":"additional","affiliation":[{"name":"Pediatrics III, West German Cancer Center University Hospital Essen  Essen Germany"},{"name":"German Cancer Consortium (DKTK) Site Essen Cancer Research Center (NCT) Cologne\u2010  Essen Germany"},{"name":"Faculty of Medicine University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiebke K.","family":"Guder","sequence":"additional","affiliation":[{"name":"German Cancer Consortium (DKTK) Site Essen Cancer Research Center (NCT) Cologne\u2010  Essen Germany"},{"name":"Faculty of Medicine University of Duisburg\u2010Essen  Essen Germany"},{"name":"Department of Orthopedic Oncology University Hospital Essen  Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arne","family":"Streitb\u00fcrger","sequence":"additional","affiliation":[{"name":"German Cancer Consortium (DKTK) Site Essen Cancer Research Center (NCT) Cologne\u2010  Essen 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