{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:14:46Z","timestamp":1791220486958,"version":"4.1.0"},"reference-count":39,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6620","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2022,11,11]]},"abstract":"<jats:p>\n            Overcoming replicative senescence is an essential step during oncogenesis, and the reactivation of\n            <jats:italic>TERT<\/jats:italic>\n            through promoter mutations is a common mechanism.\n            <jats:italic>TERT<\/jats:italic>\n            promoter mutations are acquired in about 75% of melanomas but are not sufficient to maintain telomeres, suggesting that additional mutations are required. We identified a cluster of variants in the promoter of\n            <jats:italic>ACD<\/jats:italic>\n            encoding the shelterin component TPP1.\n            <jats:italic>ACD<\/jats:italic>\n            promoter variants are present in about 5% of cutaneous melanoma and co-occur with\n            <jats:italic>TERT<\/jats:italic>\n            promoter mutations. The two most common somatic variants create or modify binding sites for E-twenty-six (ETS) transcription factors, similar to mutations in the\n            <jats:italic>TERT<\/jats:italic>\n            promoter. The variants increase the expression of\n            <jats:italic>TPP1<\/jats:italic>\n            and function together with TERT to synergistically lengthen telomeres. Our findings suggest that\n            <jats:italic>TPP1<\/jats:italic>\n            promoter variants collaborate with\n            <jats:italic>TERT<\/jats:italic>\n            activation to enhance telomere maintenance and immortalization in melanoma.\n          <\/jats:p>","DOI":"10.1126\/science.abq0607","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T18:58:42Z","timestamp":1668106722000},"page":"664-668","source":"Crossref","is-referenced-by-count":45,"title":["TPP1 promoter mutations cooperate with TERT promoter mutations to lengthen telomeres in melanoma"],"prefix":"10.1126","volume":"378","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8251-5590","authenticated-orcid":true,"given":"Pattra","family":"Chun-on","sequence":"first","affiliation":[{"name":"Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy, and Critical Care Medicine, Pittsburgh, PA, USA."},{"name":"Environmental and Occupational Health Department, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Faculty of Medicine and Public Health, Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4544-4735","authenticated-orcid":true,"given":"Angela M.","family":"Hinchie","sequence":"additional","affiliation":[{"name":"Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy, and Critical Care Medicine, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4091-538X","authenticated-orcid":true,"given":"Holly C.","family":"Beale","sequence":"additional","affiliation":[{"name":"UC Santa Cruz Genomics Institute, University of California, Santa Cruz, CA, USA."},{"name":"Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5499-8000","authenticated-orcid":true,"given":"Agustin A","family":"Gil Silva","sequence":"additional","affiliation":[{"name":"Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy, and Critical Care Medicine, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Rush","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center, Hillman Cancer Institute, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4136-1342","authenticated-orcid":true,"given":"Cindy","family":"Sander","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center, Hillman Cancer Institute, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla J.","family":"Connelly","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittani K.N.","family":"Seynnaeve","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center, Hillman Cancer Institute, Pittsburgh, PA, USA."},{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3570-4476","authenticated-orcid":true,"given":"John M.","family":"Kirkwood","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center, Hillman Cancer Institute, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1677-417X","authenticated-orcid":true,"given":"Olena M.","family":"Vaske","sequence":"additional","affiliation":[{"name":"UC Santa Cruz Genomics Institute, University of California, Santa Cruz, CA, USA."},{"name":"Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5494-8126","authenticated-orcid":true,"given":"Carol W.","family":"Greider","sequence":"additional","affiliation":[{"name":"UC Santa Cruz Genomics Institute, University of California, Santa Cruz, CA, USA."},{"name":"Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA, USA."},{"name":"Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3741-6512","authenticated-orcid":true,"given":"Jonathan K.","family":"Alder","sequence":"additional","affiliation":[{"name":"Dorothy P. and Richard P. 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