{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T16:50:03Z","timestamp":1754153403757,"version":"3.41.2"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008533","name":"Case Comprehensive Cancer Center, Case Western Reserve University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008533","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Historically classified based on histology, advances in molecular profiling have allowed further sub\u2010classification, which has improved risk stratification. Although molecular profiling has improved our understanding of disease progression and risk, the molecular evolution of therapy resistance in RMS remains poorly characterized. Transcriptomic profiling of patients with high\u2010risk, relapsed RMS was undertaken with the goal of uncovering insights into the biology of RMS treatment failure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Formalin\u2010fixed, paraffin\u2010embedded (FFPE) tissue samples from patients with relapsed RMS who had samples archived at diagnosis and relapse were obtained. Histologic subtype and PAX3\/7::FOXO1 fusion status were confirmed. Transcriptomic profiling of the FFPE tissue samples was performed using the high\u2010throughput genomics (HTG) whole transcriptome panel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 11 patients with relapsed RMS who had FFPE tissue samples archived at diagnosis and relapse following multimodality therapy. All patients were stratified as high risk, including five with PAX3\/7::FOXO1 fusion\u2010positive RMS (FP\u2010RMS) and six with PAX3\/7::FOXO1 fusion\u2010negative RMS (FN\u2010RMS). The transcriptomic analysis revealed that the myogenesis pathway and markers associated with myogenic differentiation were enriched pre\u2010treatment in patients with FP\u2010RMS and enriched post\u2010treatment in patients with FN\u2010RMS. Post\u2010treatment enrichment of the inflammatory response pathway was observed in both FP\u2010RMS and FN\u2010RMS samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Using a probe\u2010based transcriptome panel to characterize matched pre\u2010 and post\u2010treatment tissue samples from patients with RMS, we report that relapsed RMS follows a fusion status\u2010dependent evolutionary trajectory, marked by differential expression of myogenesis\u2010associated genes, myogenic differentiation markers, and inflammatory response pathways.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.31864","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T22:54:50Z","timestamp":1750978490000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic Profiling of Relapsed Rhabdomyosarcoma: Pre\u2010 and Post\u2010Treatment Tissue Analysis Reveals Molecular Characteristics of Treatment Failure"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0845-907X","authenticated-orcid":false,"given":"Andrew","family":"Muskara","sequence":"first","affiliation":[{"name":"Department of Translational Hematology and Oncology Research Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prarthana B.","family":"Parthasarathy","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology, Oncology &amp; Blood &amp; Marrow Transplantation Cleveland Clinic Children\u2019s  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4082-7945","authenticated-orcid":false,"given":"Usua","family":"Oyarbide","sequence":"additional","affiliation":[{"name":"Division of Human Biology Fred Hutch Cancer Center  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Human Biology Fred Hutch Cancer Center  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinjini","family":"Ganguly","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jarrell","family":"Imamura","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7977-3767","authenticated-orcid":false,"given":"Ross","family":"Liao","sequence":"additional","affiliation":[{"name":"Glickman Urological and Kidney Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian P.","family":"Rubin","sequence":"additional","affiliation":[{"name":"Robert J. Tomsich Pathology and Laboratory Medicine Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aidan","family":"Macaskill","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin S.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Taussig Cancer Institute at Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter M.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology, Oncology &amp; Blood &amp; Marrow Transplantation Cleveland Clinic Children\u2019s  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0130-2302","authenticated-orcid":false,"given":"Berkley E.","family":"Gryder","sequence":"additional","affiliation":[{"name":"Department of Genetics &amp; 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