{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:16:43Z","timestamp":1791908203705,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001445","name":"Alex's Lemonade Stand Foundation for Childhood Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2025,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Prognostication in pediatric and young adult osteosarcoma is typically limited to metastatic status at diagnosis and tumor necrosis after chemotherapy. Despite a complex genomic landscape, few molecular biomarkers are used clinically. This study evaluates the prognostic relevance of\n                      <jats:italic>MYC<\/jats:italic>\n                      amplification and MYC protein expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study analyzed 105 patients with high\u2010grade osteosarcoma.\n                      <jats:italic>MYC<\/jats:italic>\n                      copy number was assessed via targeted sequencing, and MYC protein expression was assessed via immunohistochemistry H score. Amplification (AMP) was defined as &gt;7 copies; high expression (EXP) was defined as an H score of &gt;150. Correlation between AMP and EXP was calculated, and overall survival (OS) was analyzed with Kaplan\u2013Meier and Cox models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the 105 patients (42% female; median age, 14 years; interquartile range, 11\u201317 years), 16% had AMP, 22% had high EXP, and 8% had both AMP and high EXP.\n                      <jats:italic>MYC<\/jats:italic>\n                      copy number positively correlated with protein expression (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a00.53;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.0001). With accounting for metastatic status, AMP and high EXP had lower OS (AMP vs. non\u2010AMP: 3\u2010year OS, 27% vs. 74%; adjusted hazard ratio [HR], 3.4; high EXP vs. low EXP: 35% vs. 77%; adjusted HR, 4.9; both\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.0001). Patients with both AMP and high EXP had markedly lower survival compared to those with non\u2010AMP and low EXP (3\u2010year OS, 0% vs. 79%; adjusted HR, 17.7;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a0.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>MYC<\/jats:italic>\n                      amplification and high protein expression both independently and concurrently predict poor survival in pediatric and young adult osteosarcoma, beyond metastatic status. Incorporating\n                      <jats:italic>MYC<\/jats:italic>\n                      status into risk stratification may enhance prognostic accuracy and inform targeted therapeutic development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.70161","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T07:15:52Z","timestamp":1762499752000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<i>MYC<\/i>\n                    amplification and MYC protein expression are poor prognostic markers in pediatric and young adult osteosarcoma"],"prefix":"10.1002","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5087-6674","authenticated-orcid":false,"given":"Matthew R.","family":"Nagy","sequence":"first","affiliation":[{"name":"Department of Pediatrics Boston Children\u2019s Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard University  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Puopolo","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber\/Boston Children\u2019s Cancer and Blood Disorders Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Alston","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Pathology Boston Children\u2019s Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreekar","family":"Challa","sequence":"additional","affiliation":[{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard University  Cambridge Massachusetts USA"},{"name":"Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelina","family":"Ceca","sequence":"additional","affiliation":[{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard University  Cambridge Massachusetts USA"},{"name":"Dana\u2010Farber\/Boston Children\u2019s Cancer and Blood Disorders Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Li","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Cherniack","sequence":"additional","affiliation":[{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard University  Cambridge Massachusetts USA"},{"name":"Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Lazo de la Vega","sequence":"additional","affiliation":[{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard University  Cambridge Massachusetts USA"},{"name":"Dana\u2010Farber\/Boston Children\u2019s Cancer and Blood Disorders Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Meyerson","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard University  Cambridge Massachusetts USA"},{"name":"Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4835-5770","authenticated-orcid":false,"given":"Alanna J.","family":"Church","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard University  Cambridge Massachusetts USA"},{"name":"Dana\u2010Farber\/Boston Children\u2019s Cancer and Blood Disorders Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Janeway","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard University  Cambridge Massachusetts USA"},{"name":"Dana\u2010Farber\/Boston Children\u2019s Cancer and Blood Disorders Center  Boston Massachusetts 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