{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T15:07:32Z","timestamp":1779030452952,"version":"3.51.4"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005009","name":"Stiftelsen Assar Gabrielssons Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016669","name":"Sj\u00f6bergstiftelsen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016669","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pleomorphic adenoma (PA) is the most common salivary gland tumor. PAs are characterized by chromosomal rearrangements of 8q12 and 12q14\u201015, leading to gene fusions involving the\n                    <jats:italic>PLAG1<\/jats:italic>\n                    and\n                    <jats:italic>HMGA2<\/jats:italic>\n                    oncogenes. Here, we performed the first comprehensive study of the transcriptomic and gene fusion landscape of 38 cytogenetically characterized PAs. RNA\u2010seq identified\n                    <jats:italic>PLAG1<\/jats:italic>\n                    or\n                    <jats:italic>HMGA2<\/jats:italic>\n                    fusions in 33\/38 cases (87%), of which 15 were novel fusions. Fusions were found also in tumors with normal karyotype, demonstrating that they are generated by cryptic rearrangements.\n                    <jats:italic>PLAG1<\/jats:italic>\n                    was mainly activated by promoter swapping and\n                    <jats:italic>HMGA2<\/jats:italic>\n                    by truncation of its 3\u2032\u2010part. RNA\u2010seq revealed upregulation of genes involved in extracellular matrix production, WNT\u2010signaling, and epithelial\u2010mesenchymal transition in PA compared to normal salivary tissue. Principal component analysis identified two PA subclusters characterized by\n                    <jats:italic>PLAG1<\/jats:italic>\n                    \u2010 and\n                    <jats:italic>HMGA2<\/jats:italic>\n                    \u2010activation, respectively, that differed in expression of genes involved in the immune system, cell adhesion, and microenvironment remodeling. Moreover, comparative analyses of PA and salivary carcinomas revealed that PA resembles myoepithelial carcinoma. Our study reveals new oncogenic gene fusions and expands our knowledge about the molecular underpinnings of PA.\n                  <\/jats:p>","DOI":"10.1002\/gcc.70023","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T07:41:23Z","timestamp":1736926883000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Transcriptomic and Gene Fusion Landscape of Pleomorphic Salivary Gland Adenomas"],"prefix":"10.1002","volume":"64","author":[{"given":"Maryam Kakay","family":"Afshari","sequence":"first","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine University of Gothenburg  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paloma","family":"Tejera Nevado","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine University of Gothenburg  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2657-1392","authenticated-orcid":false,"given":"Andr\u00e9","family":"Fehr","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Clinical Pathology Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junchi","family":"Huang","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine University of Gothenburg  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fredrik","family":"J\u00e4wert","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine University of Gothenburg  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas A.","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences University of Gothenburg  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1017-7363","authenticated-orcid":false,"given":"G\u00f6ran","family":"Stenman","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Clinical Pathology Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6391-2048","authenticated-orcid":false,"given":"Mattias K.","family":"Andersson","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine University of Gothenburg  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"185","volume-title":"World Health Organization Classification of Head and Neck Tumours","author":"Bell D.","year":"2017"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-4608(80)90030-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-4608(90)90042-9"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-4608(93)90054-P"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-4608(96)00204-X"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-013-0462-z"},{"key":"e_1_2_10_8_1","first-page":"1970","article-title":"Chromosome Translocations, Gene Fusions, and Their Molecular Consequences in Pleomorphic Salivary Gland Adenomas","volume":"10","author":"Stenman G.","year":"2022","journal-title":"Biomedicine"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0297-170"},{"key":"e_1_2_10_10_1","first-page":"13","article-title":"Expression of Reciprocal Hybrid Transcripts of HMGIC and FHIT in a Pleomorphic Adenoma of the Parotid Gland","volume":"57","author":"Geurts J. 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