{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:15:30Z","timestamp":1788952530510,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Genomic complexity and small case numbers make statistically robust assessment of mutational patterns in osteosarcoma difficult. The authors analyzed a large cohort of targeted next\u2010generation sequencing data from osteosarcoma cases from young patients submitted for clinical testing to Foundation Medicine.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n The osteosarcoma cohort included 653 patients: 109 pediatric (males, <13 years old; females, <12 years old), 246 adolescent (males, 13\u201317 years old; females, 12\u201317 years old), and 298 young adult (males and females, 18\u201340 years old). Sequencing from osteosarcoma cases was compared to a pan\u2010cancer cohort comprising 37,947 patients \u226440 years old.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Genes commonly altered and significantly enriched (\n p<\/jats:italic>\n \u00a0<\u00a0.0001) for alterations in osteosarcoma compared to other cancers were\n TP53<\/jats:italic>\n (55%),\n RB1<\/jats:italic>\n (22%),\n GID4<\/jats:italic>\n (26%),\n MYC<\/jats:italic>\n (17%), and\n CCND3<\/jats:italic>\n (16%). Less commonly altered genes also significantly enriched (\n p<\/jats:italic>\n \u00a0<\u00a0.0001) for alterations in osteosarcoma included\n AURKB<\/jats:italic>\n (odds ratio [OR], 28.0),\n NCOR1<\/jats:italic>\n (OR, 8.2), and\n BCL2L2<\/jats:italic>\n (OR, 8.9). Fisher exact tests demonstrated mutual exclusivity between\n MDM2<\/jats:italic>\n amplification and\n TP53<\/jats:italic>\n inactivation and between\n RB1<\/jats:italic>\n inactivation and\n CDK4<\/jats:italic>\n amplification or\n CDKN2A\/B<\/jats:italic>\n deletion. Chi\u2010square tests and binomial regression revealed statistically significant differences in genomic events by age, including frequent amplification of\n CDK4<\/jats:italic>\n and\n MDM2<\/jats:italic>\n in young adults and\n MYC<\/jats:italic>\n ,\n CCND3<\/jats:italic>\n , and\n CCNE1<\/jats:italic>\n in pediatric and adolescent cases.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Novel findings from this statistically rigorous analysis of a large patient population include: identifying genes of interest in osteosarcoma that are more often altered when compared to other cancers; identifying\n MYC<\/jats:italic>\n and\n CCND3<\/jats:italic>\n amplification as significantly more prevalent in osteosarcoma diagnosed in childhood; and proving mutual exclusivity and co\u2010occurrence with statistical robustness.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cncr.70500","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T15:41:24Z","timestamp":1783611684000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Analysis of a large osteosarcoma sequencing data set elucidates patterns of genomic alterations"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0914-7212","authenticated-orcid":false,"given":"Hannah G.","family":"Bousquet","sequence":"first","affiliation":[{"name":"Dana\u2010Farber\/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Kuang","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena Lazo de la","family":"Vega","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber\/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelina","family":"Ceca","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber\/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Schiantarelli","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber\/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Honecker","sequence":"additional","affiliation":[{"name":"Foundation Medicine GmbH Penzberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C.","family":"Hiemenz","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne J.","family":"Forrest","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber\/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Janeway","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber\/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34163"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra2103423"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.03.003"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15936"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.cd\u201017\u20101152"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201014646\u2010w"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/po.22.00334"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2012.43.8598"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2696"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009843107"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc2213457"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.ccr\u201018\u20104032"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201034689\u20105"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.835004"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201030453\u2010x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201030496\u20100"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000451046"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjp2.219"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2023.02.009"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535\u20107163.targ\u201023\u2010pr008"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.70500","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncr.70500","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.70500","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:38:45Z","timestamp":1788950325000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.70500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":20,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2026,7,15]]}},"alternative-id":["10.1002\/cncr.70500"],"URL":"https:\/\/doi.org\/10.1002\/cncr.70500","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]},"assertion":[{"value":"2025-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70500"}}