{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:09:35Z","timestamp":1792894175731,"version":"4.5.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"44","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,11,3]]},"abstract":"<jats:p>\n                    The transcription factor gene\n                    <jats:italic>MYB<\/jats:italic>\n                    was identified recently as an oncogene that is rearranged\/duplicated in some human leukemias. Here we describe a new mechanism of activation of\n                    <jats:italic>MYB<\/jats:italic>\n                    in human cancer involving gene fusion. We show that the t(6;9)(q22\u201323;p23\u201324) translocation in adenoid cystic carcinomas (ACC) of the breast and head and neck consistently results in fusions encoding chimeric transcripts predominantly consisting of\n                    <jats:italic>MYB<\/jats:italic>\n                    exon 14 linked to the last coding exon(s) of\n                    <jats:italic>NFIB<\/jats:italic>\n                    . The minimal common part of\n                    <jats:italic>MYB<\/jats:italic>\n                    deleted as the result of fusion was exon 15 including the 3\u2032-UTR, which contains several highly conserved target sites for miR-15a\/16 and miR-150 microRNAs. These microRNAs recently were shown to regulate\n                    <jats:italic>MYB<\/jats:italic>\n                    expression negatively. We suggest that deletion of these target sites may disrupt repression of\n                    <jats:italic>MYB<\/jats:italic>\n                    leading to overexpression of\n                    <jats:italic>MYB-NFIB<\/jats:italic>\n                    transcripts and protein and to activation of critical\n                    <jats:italic>MYB<\/jats:italic>\n                    targets, including genes associated with apoptosis, cell cycle control, cell growth\/angiogenesis, and cell adhesion. Forced overexpression of miR-15a\/16 and miR-150 in primary fusion-positive ACC cells did not significantly alter the expression of\n                    <jats:italic>MYB<\/jats:italic>\n                    as compared with leukemic cells with\n                    <jats:italic>MYB<\/jats:italic>\n                    activation\/duplication. Our data indicate that the\n                    <jats:italic>MYB-NFIB<\/jats:italic>\n                    fusion is a hallmark of ACC and that deregulation of the expression of\n                    <jats:italic>MYB<\/jats:italic>\n                    and its target genes is a key oncogenic event in the pathogenesis of ACC. Our findings also suggest that the gain-of-function activity resulting from the\n                    <jats:italic>MYB-NFIB<\/jats:italic>\n                    fusion is a candidate therapeutic target.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0909114106","type":"journal-article","created":{"date-parts":[[2009,10,19]],"date-time":"2009-10-19T21:44:12Z","timestamp":1255988652000},"page":"18740-18744","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":743,"title":["Recurrent fusion of\n                    <i>MYB<\/i>\n                    and\n                    <i>NFIB<\/i>\n                    transcription factor genes in carcinomas of the breast and head and neck"],"prefix":"10.1073","volume":"106","author":[{"given":"Marta","family":"Persson","sequence":"first","affiliation":[{"name":"Lundberg Laboratory for Cancer Research, Department of Pathology, the Sahlgrenska Academy at University of Gothenburg, SE-413 45 Gothenburg, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ywonne","family":"Andr\u00e9n","sequence":"additional","affiliation":[{"name":"Lundberg Laboratory for Cancer Research, Department of Pathology, the Sahlgrenska Academy at University of Gothenburg, SE-413 45 Gothenburg, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Mark","sequence":"additional","affiliation":[{"name":"Department of Pathology, Central Hospital, SE-541 85 Sk\u00f6vde, Sweden; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo M.","family":"Horlings","sequence":"additional","affiliation":[{"name":"Division of Experimental Therapy, The Netherlands Cancer Institute, 1066CX, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Persson","sequence":"additional","affiliation":[{"name":"Lundberg Laboratory for Cancer Research, Department of Pathology, the Sahlgrenska Academy at University of Gothenburg, SE-413 45 Gothenburg, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran","family":"Stenman","sequence":"additional","affiliation":[{"name":"Lundberg Laboratory for Cancer Research, Department of Pathology, the Sahlgrenska Academy at University of Gothenburg, SE-413 45 Gothenburg, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,11,3]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nrc2091","article-title":"The impact of translocations and gene fusions on cancer causation","volume":"7","author":"Mitelman F","year":"2007","unstructured":"F Mitelman, B Johansson, F Mertens, The impact of translocations and gene fusions on cancer causation. 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