{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T21:44:40Z","timestamp":1775771080389,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"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: Nasopharyngeal carcinoma (NPC) is a rare head and neck cancer arising from the mucosal lining of the nasopharynx, for which systemic therapeutic options remain scarce, reflecting the limited characterization of its genomic profile. This study utilized a large patient-level genomic repository to characterize genetic alterations, identify potential therapeutic targets, and improve disease modeling in NPC. Methods: A retrospective analysis of NPC 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 identified in KMT2D (20%), TP53 (16%), CYLD (9.6%), NFKBIA (6.4%), and PIK3CA (5.6%), implicating the p53, NF-\u03baB, and PI3K pathways in NPC development. Notably, significantly distinct mutational profiles were observed based on both sex and race, with female patients exhibiting higher frequencies of PIK3C2G, ETV6, and CDKN1B mutations and non-Asian patients showing enrichment in KDM5A, CCND2, and TP53 mutations. Conclusions: This study presents a detailed genomic profile of NPC, identifying key mutations within established cancer-associated pathways. The identification of frequently mutated pathways (p53, NF-\u03baB, and PI3K) suggests potential targets for novel therapies. Furthermore, distinct mutational landscapes in female and Asian NPC patients offer possibilities for precision therapeutic interventions.<\/jats:p>","DOI":"10.3390\/cancers17091544","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T05:10:32Z","timestamp":1746076232000},"page":"1544","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molecular Profiling of Nasopharyngeal Carcinoma Using the AACR Project GENIE Repository"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6403-502X","authenticated-orcid":false,"given":"Beau","family":"Hsia","sequence":"first","affiliation":[{"name":"School of Medicine, Creighton University, Phoenix, AZ 85012, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2582-9855","authenticated-orcid":false,"given":"Asritha","family":"Sure","sequence":"additional","affiliation":[{"name":"School of Medicine, Boston University, Boston, MA 02118, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8589-086X","authenticated-orcid":false,"given":"Roshan","family":"Dongre","sequence":"additional","affiliation":[{"name":"School of Engineering Medicine, Texas A&M University, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Jo","sequence":"additional","affiliation":[{"name":"Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Kuzniar","sequence":"additional","affiliation":[{"name":"Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Bitar","sequence":"additional","affiliation":[{"name":"School of Medicine, Creighton University, Phoenix, AZ 85012, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saif A.","family":"Alshaka","sequence":"additional","affiliation":[{"name":"School of Medicine, Creighton University, Phoenix, AZ 85012, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6691-3174","authenticated-orcid":false,"given":"Jeeho D.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Naval Medical Center San Diego, San Diego, CA 92134, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bastien A.","family":"Valencia-Sanchez","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic Florida, Jacksonville, FL 32224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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-Rady Children\u2019s Hospital, San Diego, CA 92123, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael L.","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of California San Diego-Rady Children\u2019s Hospital, San Diego, CA 92123, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8145-1721","authenticated-orcid":false,"given":"Vijay A.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, San Diego, CA 92093, USA"},{"name":"Division of Pediatric Otolaryngology, Rady Children\u2019s Hospital, San Diego, CA 92123, 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