{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T19:20:55Z","timestamp":1775935255131,"version":"3.50.1"},"reference-count":142,"publisher":"American Association for Cancer Research (AACR)","issue":"4","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Telomerase (TERT) activation is a fundamental step in tumorigenesis. By maintaining telomere length, telomerase relieves a main barrier on cellular lifespan, enabling limitless proliferation driven by oncogenes. The recently discovered, highly recurrent mutations in the promoter of TERT are found in over 50 cancer types, and are the most common mutation in many cancers. Transcriptional activation of TERT, via promoter mutation or other mechanisms, is the rate-limiting step in production of active telomerase. Although TERT is expressed in stem cells, it is naturally silenced upon differentiation. Thus, the presence of TERT promoter mutations may shed light on whether a particular tumor arose from a stem cell or more differentiated cell type. It is becoming clear that TERT mutations occur early during cellular transformation, and activate the TERT promoter by recruiting transcription factors that do not normally regulate TERT gene expression. This review highlights the fundamental and widespread role of TERT promoter mutations in tumorigenesis, including recent progress on their mechanism of transcriptional activation. These somatic promoter mutations, along with germline variation in the TERT locus also appear to have significant value as biomarkers of patient outcome. Understanding the precise molecular mechanism of TERT activation by promoter mutation and germline variation may inspire novel cancer cell-specific targeted therapies for a large number of cancer patients. Mol Cancer Res; 14(4); 315\u201323. \u00a92016 AACR.<\/jats:p>","DOI":"10.1158\/1541-7786.mcr-16-0003","type":"journal-article","created":{"date-parts":[[2016,3,4]],"date-time":"2016-03-04T04:24:57Z","timestamp":1457065497000},"page":"315-323","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":274,"title":["Understanding TERT Promoter Mutations: A Common Path to Immortality"],"prefix":"10.1158","volume":"14","author":[{"given":"Robert J.A.","family":"Bell","sequence":"first","affiliation":[{"name":"1Department of Neurological Surgery, University of California, San Francisco, California."}]},{"given":"H. Tomas","family":"Rube","sequence":"additional","affiliation":[{"name":"2Department of Biological Sciences, Columbia University, New York, New York."}]},{"given":"Ana","family":"Xavier-Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"1Department of Neurological Surgery, University of California, San Francisco, California."},{"name":"3Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal."},{"name":"4ICVS\/3B's-PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Braga, Portugal."}]},{"given":"Bruno M.","family":"Costa","sequence":"additional","affiliation":[{"name":"3Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal."},{"name":"4ICVS\/3B's-PT Government Associate Laboratory, Braga\/Guimar\u00e3es, Braga, Portugal."}]},{"given":"Andrew","family":"Mancini","sequence":"additional","affiliation":[{"name":"1Department of Neurological Surgery, 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