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We have previously shown that the <jats:italic>PLAG1<\/jats:italic> and <jats:italic>HMGA2<\/jats:italic> oncogenes are the targets of these rearrangements. Here, we have identified previously unrecognized subsets of PAs with ins(9;8)\/t(8;9) (n = 5) and ins(9;12)\/t(9;12) (n = 8) and breakpoints located in the vicinity of the <jats:italic>PLAG1<\/jats:italic> and <jats:italic>HMGA2<\/jats:italic> loci. RNA\u2010sequencing and reverse transcriptase (RT)\u2010PCR analyses of a case with an ins(9;8) revealed a novel <jats:italic>NFIB\u2010PLAG1<\/jats:italic> fusion in which <jats:italic>NFIB<\/jats:italic> exon 4 is linked to <jats:italic>PLAG1<\/jats:italic> exon 3. In contrast to the developmentally regulated <jats:italic>PLAG1<\/jats:italic> gene, <jats:italic>NFIB<\/jats:italic> was highly expressed in normal salivary gland, indicating that <jats:italic>PLAG1<\/jats:italic> in this case, as in other variant fusions, is activated by promoter swapping. RT\u2010PCR analysis of three PAs with t(9;12) revealed two tumors with chimeric transcripts consisting of <jats:italic>HMGA2<\/jats:italic> exon 4 linked to <jats:italic>NFIB<\/jats:italic> exons 9 or 3 and one case with a fusion linking <jats:italic>HMGA2<\/jats:italic> exon 3 to <jats:italic>NFIB<\/jats:italic> exon 9. The <jats:italic>NFIB<\/jats:italic> fusion events resulted in potent activation of <jats:italic>PLAG1<\/jats:italic> and <jats:italic>HMGA2<\/jats:italic>. Analysis of the chromatin landscape surrounding <jats:italic>NFIB<\/jats:italic> revealed several super\u2010enhancers in the 5\u2032\u2010 and 3\u2032\u2010parts of the <jats:italic>NFIB<\/jats:italic> locus and its flanking sequences. These findings indicate that <jats:italic>PLAG1<\/jats:italic> and <jats:italic>HMGA2<\/jats:italic>, similar to <jats:italic>MYB<\/jats:italic> in adenoid cystic carcinoma, may be activated by enhancer\u2010hijacking events, in which super\u2010enhancers in <jats:italic>NFIB<\/jats:italic> are translocated upstream of <jats:italic>PLAG1<\/jats:italic> or downstream of <jats:italic>HMGA2<\/jats:italic>. Our results further emphasize the role of <jats:italic>NFIB<\/jats:italic> as a fusion partner to multiple oncogenes in histopathologically different types of salivary gland tumors.<\/jats:p>","DOI":"10.1002\/gcc.22885","type":"journal-article","created":{"date-parts":[[2020,7,12]],"date-time":"2020-07-12T18:50:02Z","timestamp":1594579802000},"page":"652-660","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Activation of <scp><i>PLAG1<\/i><\/scp> and <scp><i>HMGA2<\/i><\/scp> by gene fusions involving the transcriptional regulator gene <scp><i>NFIB<\/i><\/scp>"],"prefix":"10.1002","volume":"59","author":[{"given":"Maryam Kakay","family":"Afshari","sequence":"first","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Pathology University of Gothenburg, Sahlgrenska University Hospital  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 Pathology University of Gothenburg, Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paloma Tejera","family":"Nevado","sequence":"additional","affiliation":[{"name":"Sahlgrenska Center for Cancer Research, Department of Pathology University of Gothenburg, 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 Pathology University of Gothenburg, Sahlgrenska University Hospital  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 Pathology University of Gothenburg, Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,8,5]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"185","volume-title":"World Health Organization Classification of Head and Neck Tumours","author":"Bell 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