{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:58:42Z","timestamp":1787237922051,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Chordoma is a rare primary tumor originating from embryonic notochord remnants, with limited systemic therapeutic options due to a poor understanding of its genomic landscape. This study aims to characterize the genetic alterations in chordoma using a large national patient-level genomic repository, the AACR Project GENIE, to identify potential therapeutic targets and improve disease modeling. Methods: A retrospective analysis of chordoma samples was conducted using the AACR Project GENIE database. Targeted sequencing data were analyzed for recurrent somatic mutations, tumor mutational burden, and chromosomal copy number variations, with significance set at p &lt; 0.05. Results: Frequent mutations were observed in genes associated with SWI\/SNF complex affecting chromatin remodeling (SETD2, PBRM1, ARID1A). Mutations were also common among the TERT promoter regions, and cell cycle regulation (CDKN2A). Significant co-occurrences were identified among PBRM1, BRCA2, and KMT2D mutations. CDKN2A\/B deletions were enriched in metastatic tumors, and pediatric cases demonstrated distinct mutation profiles compared to adults. Conclusions: This study provides a genomic profile of chordoma, identifying key mutations and potential therapeutic targets. These findings highlight the roles of chromatin remodeling and cell cycle pathways in chordoma biology, offering insights for future precision medicine approaches and therapeutic interventions.<\/jats:p>","DOI":"10.3390\/cancers17030536","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T10:09:52Z","timestamp":1738750192000},"page":"536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genomic Characterization of Chordoma: Insights from the AACR Project GENIE Database"],"prefix":"10.3390","volume":"17","author":[{"given":"Beau","family":"Hsia","sequence":"first","affiliation":[{"name":"School of Medicine, Creighton University, Phoenix, AZ 85012, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Bitar","sequence":"additional","affiliation":[{"name":"School of Medicine, Creighton University, Phoenix, AZ 85012, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saif A.","family":"Alshaka","sequence":"additional","affiliation":[{"name":"School of Medicine, Creighton University, Phoenix, AZ 85012, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6691-3174","authenticated-orcid":false,"given":"Jeeho D.","family":"Kim","sequence":"additional","affiliation":[{"name":"Naval Medical Center San Diego, Department of Otolaryngology-Head and Neck Surgery, San Diego, CA 92134, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastien A.","family":"Valencia-Sanchez","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, Mayo Clinic Florida, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhoud","family":"Faraji","sequence":"additional","affiliation":[{"name":"Division of Pediatric Otolaryngology, Rady Children\u2019s Hospital, San Diego, CA 92123, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7422-390X","authenticated-orcid":false,"given":"Michael G.","family":"Brandel","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of California San Diego\u2014Rady Children\u2019s Hospital, San Diego, CA 92123, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4748-4634","authenticated-orcid":false,"given":"Mariko","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Children\u2019s Hospital of Orange County, Orange, CA 92868, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Ross","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neurology, Children\u2019s Hospital Orange County, University of California Irvine, Orange, CA 92868, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of California San Diego\u2014Rady Children\u2019s Hospital, San Diego, CA 92123, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8145-1721","authenticated-orcid":false,"given":"Vijay A.","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Pediatric Otolaryngology, Rady Children\u2019s Hospital, San Diego, CA 92123, USA"},{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, University of California San Diego, San Diego, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3229-5021","authenticated-orcid":false,"given":"Sean P.","family":"Polster","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1159\/000509386","article-title":"Skull Base Chordomas and Chondrosarcomas","volume":"110","author":"Kremenevski","year":"2020","journal-title":"Neuroendocrinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1023\/A:1008947301735","article-title":"Chordoma: Incidence and Survival Patterns in the United States, 1973\u20131995","volume":"12","author":"McMaster","year":"2001","journal-title":"Cancer Causes Control"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s11060-020-03511-x","article-title":"Descriptive Epidemiology of Chordomas in the United States","volume":"148","author":"Das","year":"2020","journal-title":"J. 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