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Histological grading is the primary tool for predicting clinical outcomes in conventional chondrosarcoma. However, its high interobserver variability limits reliable distinction between low\u2010 and high\u2010risk patients, potentially leading to suboptimal clinical management. Given the increasing use of DNA methylation profiling as a valuable tool in surgical pathology for tumor classification, we investigated its prognostic value in central conventional chondrosarcoma. We generated methylation data from 69 primary central conventional chondrosarcomas profiled with Illumina's\n                    <jats:italic>Human MethylationEPIC Array<\/jats:italic>\n                    (850\u2009k sites), and identified methylation sites individually linked to patient outcome. A LASSO Cox regression model was applied to these methylation sites to identify an optimal set of eight informative sites. With the regression coefficients of these methylation sites, we constructed a risk score that predicts central conventional Chondrosarcoma Risk Outcome from Methylation (CHROME). CHROME stratifies patients into\n                    <jats:italic>High<\/jats:italic>\n                    or\n                    <jats:italic>Low risk<\/jats:italic>\n                    groups for disease recurrence, onset of metastasis and disease\u2010specific mortality. Survival analysis in an independent validation cohort (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200968) demonstrated strong discriminatory performance of CHROME, with complete separation of outcomes and no adverse events observed in the\n                    <jats:italic>Low risk<\/jats:italic>\n                    group. Overview of the clinico\u2010pathological information showed that a low grade (ACT\/G1) case with an event was correctly assigned to the\n                    <jats:italic>High risk<\/jats:italic>\n                    group, while nine high grade cases without events were classified as\n                    <jats:italic>Low risk<\/jats:italic>\n                    . CHROME provides accurate risk stratification in central conventional chondrosarcoma and may represent a valuable tool for improving its prognostication and clinical management.\n                  <\/jats:p>","DOI":"10.1002\/gcc.70160","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:19:02Z","timestamp":1785903542000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Accurate Prediction of Central Conventional Chondrosarcoma Risk and Outcome Using Methylation Profiling:\n                    <scp>CHROME<\/scp>"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0698-2212","authenticated-orcid":false,"given":"Sara","family":"Cardoso","sequence":"first","affiliation":[{"name":"Department of Pathology Leiden University Medical Center  Leiden the Netherlands"},{"name":"Leiden Center for Computational Oncology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5913-7413","authenticated-orcid":false,"given":"Baptiste","family":"Ameline","sequence":"additional","affiliation":[{"name":"Bone Tumor Reference Center at the Institute of Pathology University Hospital Basel and University Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4067-9818","authenticated-orcid":false,"given":"Sanne","family":"Venneker","sequence":"additional","affiliation":[{"name":"Department of Pathology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora M.","family":"Meijer","sequence":"additional","affiliation":[{"name":"Department of Pathology Leiden University Medical Center  Leiden the Netherlands"},{"name":"Leiden Center for Computational Oncology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep B.","family":"Erdem","sequence":"additional","affiliation":[{"name":"Department of Pathology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Ruano","sequence":"additional","affiliation":[{"name":"Department of Pathology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendy E.","family":"van den Akker","sequence":"additional","affiliation":[{"name":"Department of Pathology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9048-4867","authenticated-orcid":false,"given":"Anne\u2010Marie","family":"Cleton\u2010Jansen","sequence":"additional","affiliation":[{"name":"Department of Pathology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7914-1118","authenticated-orcid":false,"given":"Jon","family":"Brugger","sequence":"additional","affiliation":[{"name":"Bone Tumor Reference Center at the Institute of Pathology University Hospital Basel and University Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge H.","family":"Briaire\u2010de Bruijn","sequence":"additional","affiliation":[{"name":"Department of Pathology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire H. J.","family":"Scholte","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9156-7656","authenticated-orcid":false,"given":"Michiel A. J.","family":"van de Sande","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7015-3841","authenticated-orcid":false,"given":"Felix Haglund","family":"de Flon","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology and Cancer Diagnostics Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Baumhoer","sequence":"additional","affiliation":[{"name":"Bone Tumor Reference Center at the Institute of Pathology University Hospital Basel and University Basel  Basel Switzerland"},{"name":"Basel Research Centre for Child Health  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6122-1024","authenticated-orcid":false,"given":"Noel F. C. 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Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.70160","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/gcc.70160","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.70160","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:26:05Z","timestamp":1787837165000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.70160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":50,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/gcc.70160"],"URL":"https:\/\/doi.org\/10.1002\/gcc.70160","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2026-05-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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