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However, our understanding of DNA demethylation in cancer biology and its clinical significance remain limited. This study showed that TET1 expression correlated with poor survival in advanced\u2010stage epithelial ovarian carcinoma (EOC), and with cell migration, anchorage\u2010independent growth, cancer stemness, and tumorigenicity. In particular, TET1 was highly expressed in serous tubal intraepithelial carcinoma (STIC), a currently accepted type II EOC precursor, and inversely correlated with <jats:italic>TP53<\/jats:italic> mutations. Moreover, TET1 could demethylate the epigenome and activate multiple oncogenic pathways, including an immunomodulation network having casein kinase II subunit alpha (CK2\u03b1) as a hub. Patients with <jats:italic>TET1<\/jats:italic><jats:sup>high<\/jats:sup><jats:italic>CK2\u03b1<\/jats:italic><jats:sup>high<\/jats:sup> EOCs had the worst outcomes, and TET1\u2010expressing EOCs were more sensitive to a CK2 inhibitor, both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Our findings uncover the oncogenic and poor prognostic roles of TET1 in EOC and suggest an unexplored role of epigenetic reprogramming in early ovarian carcinogenesis. Moreover, the immunomodulator CK2\u03b1 represents a promising new therapeutic target, warranting clinical trials of the tolerable CK2 inhibitor, CX4945, for precision medicine against EOC. Copyright \u00a9 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.5266","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T19:57:46Z","timestamp":1552939066000},"page":"363-376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["TET1 reprograms the epithelial ovarian cancer epigenome and reveals casein kinase 2\u03b1 as a therapeutic target"],"prefix":"10.1002","volume":"248","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4870-3664","authenticated-orcid":false,"given":"Lin\u2010Yu","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate Institute of Life Sciences National Defense Medical Center  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6458-4672","authenticated-orcid":false,"given":"Rui\u2010Lan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and 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