{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T20:27:01Z","timestamp":1789244821466,"version":"build-2803163510"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T00:00:00Z","timestamp":1687564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22\u00a0K09662"],"award-info":[{"award-number":["22\u00a0K09662"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Due to the diversity of histopathologic types in salivary gland carcinoma, genomic analysis of large cohorts with next-generation sequencing by histologic type has not been adequately performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We analysed data from 93 patients with salivary duct carcinoma and 243 patients with adenoid cystic carcinoma who underwent comprehensive genomic profiling testing in the Center for Cancer Genomics and Advanced Therapeutics database, a Japanese national genome profiling database. We visualised gene mutation profiles using the OncoPrinter platform. Fisher\u2019s exact test, Kaplan\u2013Meier analysis, log-rank test and Cox regression models were used for statistical analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In salivary duct carcinoma, a population with CDK12 and ERBB2 co-amplification was detected in 20 of 37 (54.1%) patients with ERBB2 amplification. We identified five loss-of-function variants in genes related to homologous recombination deficiency, such as BRCA2 and CDK12. Cox survival analysis showed that CDK12 and ERBB2 co-amplification is associated with overall survival (hazard ratio, 3.597; P\u00a0=\u00a00.045). In salivary duct carcinoma, NOTCH1 mutations were the most common, followed by mutations in chromatin modification genes such as KMT2D, BCOR, KDM6A, ARID1A, EP300 and CREBBP. In the multivariate Cox analysis, activating NOTCH1 mutations (hazard ratio, 3.569; P\u00a0=\u00a00.009) and ARID1A mutations (hazard ratio, 4.029; P\u00a0=\u00a00.034) were significantly associated with overall survival.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>CDK12 and ERBB2 co-amplification is associated with a poor prognosis in salivary duct carcinoma. Chromatin remodelling genes are deeply involved in tumour progression in adenoid cystic carcinoma. One such gene, ARID1A, was an independent prognostic factor. In salivary duct carcinoma and adenoid cystic carcinoma, there might be minor populations with mutations that could be targeted for treatment with the synthetic lethality approach.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jjco\/hyad066","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T09:56:16Z","timestamp":1687773376000},"page":"798-807","source":"Crossref","is-referenced-by-count":13,"title":["<i>CDK12<\/i> alterations and <i>ARID1A<\/i> mutations are predictors of poor prognosis and therapeutic targets in high-grade salivary gland carcinoma: analysis of the National Genomic Profiling Database"],"prefix":"10.1093","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5823-3718","authenticated-orcid":false,"given":"Kenya","family":"Kobayashi","sequence":"first","affiliation":[{"name":"The University of Tokyo Department of Otolaryngology, Head and Neck Surgery, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Saito","sequence":"additional","affiliation":[{"name":"The University of Tokyo Department of Otolaryngology, Head and Neck Surgery, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3658-4442","authenticated-orcid":false,"given":"Hidenori","family":"Kage","sequence":"additional","affiliation":[{"name":"The University of Tokyo Department of Next-Generation Precision Medicine Development Laboratory, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Fukuoka","sequence":"additional","affiliation":[{"name":"The University of Tokyo Department of Otolaryngology, Head and Neck Surgery, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Yamamura","sequence":"additional","affiliation":[{"name":"The University of Tokyo Department of Otolaryngology, Head and Neck Surgery, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Mukai","sequence":"additional","affiliation":[{"name":"The University of Tokyo Department of Otolaryngology, Head and Neck Surgery, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2468-9573","authenticated-orcid":false,"given":"Katsutoshi","family":"Oda","sequence":"additional","affiliation":[{"name":"The University of Tokyo Department of Integrative Genomics, Graduate School of Medicine, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Yamasoba","sequence":"additional","affiliation":[{"name":"The University of Tokyo Department of Otolaryngology, Head and Neck Surgery, , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,24]]},"reference":[{"key":"2023090116055914500_ref1","volume-title":"Tumors of the Salivary Gland (AFIP atlas of tumor & non-tumor pathology, 5th series, fascicle 5)","author":"Justin","year":"2021"},{"key":"2023090116055914500_ref2","doi-asserted-by":"crossref","first-page":"4623","DOI":"10.1158\/1078-0432.CCR-16-0637","article-title":"Comprehensive molecular characterization of salivary duct carcinoma reveals actionable targets and similarity to arocrine breast cancer","volume":"22","author":"Dalin","year":"2016","journal-title":"Clin Cancer Res"},{"key":"2023090116055914500_ref3","doi-asserted-by":"crossref","first-page":"7322","DOI":"10.1002\/cam4.2602","article-title":"Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling","volume":"8","author":"Gargano","year":"2019","journal-title":"Cancer Med"},{"key":"2023090116055914500_ref4","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1002\/cncr.30179","article-title":"Subsets of salivary duct carcinoma defined by morphologic evidence of pleomorphic adenoma. 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