{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:57:20Z","timestamp":1791327440720,"version":"4.3.1"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,9,14]],"date-time":"2012-09-14T00:00:00Z","timestamp":1347580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cervical cancer results from persistent infection with high\u2010risk human papillomavirus (hrHPV). Common genetic aberrations in cervical (pre)cancers encompass large genomic regions with numerous genes, hampering identification of driver genes. This study aimed to identify genes functionally involved in HPV\u2010mediated transformation by analysis of focal aberrations (&lt;3 Mb) in high\u2010grade cervical intraepithelial neoplasia (hgCIN). Focal chromosomal aberrations were determined in high\u2010resolution array comparative genomic hybridization data of 60 hgCIN. Genes located within focal aberrations were validated using 2 external gene expression datasets or qRT\u2010PCR. Functional roles of candidate genes <jats:italic>EYA2<\/jats:italic> (20q13) and <jats:italic>hsa\u2010miR\u2010375<\/jats:italic> (2q35) were studied by siRNA\u2010mediated knock\u2010down and overexpression, respectively, in hrHPV\u2010containing cell lines. We identified 74 focal aberrations encoding 305 genes. Concurrent altered expression in hgCIN and\/or cervical carcinomas compared with normal cervical samples was shown for <jats:italic>ATP13A3, HES1, OPA1, HRASLS, EYA2, ZMYND8, APOBEC2<\/jats:italic>, and <jats:italic>NCR2<\/jats:italic>. Gene silencing of <jats:italic>EYA2<\/jats:italic> significantly reduced viability, migratory capacity, and anchorage\u2010independent growth of HPV16\u2010transformed keratinocytes. For <jats:italic>hsa\u2010miR\u2010375<\/jats:italic>, a direct correlation between a (focal) loss and significantly reduced expression was found. Downregulation of <jats:italic>hsa\u2010miR\u2010375<\/jats:italic> expression was confirmed in an independent series of cervical tissues. Ectopic expression of <jats:italic>hsa\u2010miR\u2010375<\/jats:italic> in 2 cervical carcinoma cell lines reduced cellular viability. Our data provide a proof of concept that chromosomal aberrations are actively contributing to HPV\u2010induced carcinogenesis and identify <jats:italic>EYA2<\/jats:italic> and <jats:italic>hsa\u2010miR\u2010375<\/jats:italic> as oncogene and tumor suppressor gene, respectively. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.22006","type":"journal-article","created":{"date-parts":[[2012,9,15]],"date-time":"2012-09-15T05:07:15Z","timestamp":1347685635000},"page":"56-68","source":"Crossref","is-referenced-by-count":82,"title":["Focal aberrations indicate <i>EYA2<\/i> and <i>hsa\u2010miR\u2010375<\/i> as oncogene and tumor suppressor in cervical carcinogenesis"],"prefix":"10.1002","volume":"52","author":[{"given":"Mariska","family":"Bierkens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Krijgsman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia M.","family":"Wilting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leontien","family":"Bosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelieke","family":"Jaspers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerrit A.","family":"Meijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris J. 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