{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T22:00:04Z","timestamp":1787263204314,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T00:00:00Z","timestamp":1523923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["2611892"],"award-info":[{"award-number":["2611892"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"MIUR","doi-asserted-by":"publisher","award":["PON03PE_00060_7"],"award-info":[{"award-number":["PON03PE_00060_7"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:p>Two recurrent mutations (\u2013124 G\u2009&gt;\u2009A and \u2212146 G\u2009&gt;\u2009A) in the core promoter region of the human telomerase reverse transcriptase (<jats:italic>TERT<\/jats:italic>) gene create consensus binding sites for ETS transcription factors and cause increased <jats:italic>TERT<\/jats:italic> expression in several tumour types. We analyzed <jats:italic>TERT<\/jats:italic> promoter mutations and <jats:italic>TERT<\/jats:italic> mRNA levels in head and neck cancer, cervical carcinoma and cervical intraepithelial neoplasia (CIN) as well as in C\u20104I, CaSki, HeLa and SiHa cervical cell lines. Nucleotide sequence analysis of <jats:italic>TERT<\/jats:italic> promoter region showed that 33.3% of oral squamous cell carcinoma (SCC) and 16.8% of cervical SCC harboured mutually exclusive G to A transitions at nucleotide position \u2212124 or \u2212146. <jats:italic>TERT<\/jats:italic> promoter was mutated at nucleotide \u2212146 (G\u2009&gt;\u2009A) in SiHa cell line. Other nucleotide changes creating in some cases putative ETS binding sites were more frequent in oral SCC (26.7%) than in cervical carcinoma (4.8%). The frequency of mutations was independent of human papillomavirus (HPV) tumour status in both cervical and oral cancer. Expression of <jats:italic>TERT<\/jats:italic> gene was significantly higher in <jats:italic>TERT<\/jats:italic> promoter mutated (\u2013124G\u2009&gt;\u2009A or \u2212146G\u2009&gt;\u2009A) cervical SCC compared to not mutated SCC irrespective of HPV16 E6 and E7 levels. Such hot spot changes were not detected in oropharyngeal SCC, cervical adenocarcinoma and CIN lesions. Our results suggest that <jats:italic>TERT<\/jats:italic> promoter mutations play a relevant role in oral SCC as well as in cervical SCC, besides the already known effect of HPV16 E6 protein on <jats:italic>TERT<\/jats:italic> expression.<\/jats:p>","DOI":"10.1002\/ijc.31412","type":"journal-article","created":{"date-parts":[[2018,3,31]],"date-time":"2018-03-31T11:27:58Z","timestamp":1522495678000},"page":"1153-1161","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Distinct profiles of <i>TERT<\/i> promoter mutations and telomerase expression in head and neck cancer and cervical carcinoma"],"prefix":"10.1002","volume":"143","author":[{"given":"Clorinda","family":"Annunziata","sequence":"first","affiliation":[{"name":"Molecular Biology and Viral Oncology Unit Istituto Nazionale Tumori IRCCS \u201cFondazione G. Pascale\u201d Napoli 80131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pezzuto","sequence":"additional","affiliation":[{"name":"Molecular Biology and Viral Oncology Unit Istituto Nazionale Tumori IRCCS \u201cFondazione G. Pascale\u201d Napoli 80131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Greggi","sequence":"additional","affiliation":[{"name":"Gynecology Oncology Unit Istituto Nazionale Tumori IRCCS \u201cFondazione G. Pascale\u201d Napoli 80131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Ionna","sequence":"additional","affiliation":[{"name":"Maxillofacial and Ear Nose and Throat Surgery Department Istituto Nazionale Tumori IRCCS \u201cFondazione G. Pascale\u201d Napoli 80131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Losito","sequence":"additional","affiliation":[{"name":"Department of Pathology Istituto Nazionale Tumori IRCCS \u201cFondazione G. Pascale\u201d Napoli 80131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Botti","sequence":"additional","affiliation":[{"name":"Department of Pathology Istituto Nazionale Tumori IRCCS \u201cFondazione G. Pascale\u201d Napoli 80131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Buonaguro","sequence":"additional","affiliation":[{"name":"Molecular Biology and Viral Oncology Unit Istituto Nazionale Tumori IRCCS \u201cFondazione G. Pascale\u201d Napoli 80131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco M.","family":"Buonaguro","sequence":"additional","affiliation":[{"name":"Molecular Biology and Viral Oncology Unit Istituto Nazionale Tumori IRCCS \u201cFondazione G. Pascale\u201d Napoli 80131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3523-3264","authenticated-orcid":false,"given":"Maria Lina","family":"Tornesello","sequence":"additional","affiliation":[{"name":"Molecular Biology and Viral Oncology Unit Istituto Nazionale Tumori IRCCS \u201cFondazione G. Pascale\u201d Napoli 80131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,17]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"FerlayJ SoerjomataramI ErvikM et al. GLOBOCAN 2012 v1.0 cancer incidence and mortality worldwide: IARC CancerBase No. 11. Lyon France: International Agency for Research on Cancer 2013."},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25019"},{"key":"e_1_2_6_4_1","first-page":"4550","article-title":"Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers","volume":"31","author":"Chaturvedi AK","year":"2013","journal-title":"J Clin Orthod"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27410"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2013.04.024"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30716"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2017.07.007"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx304"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm453"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2014.06.003"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2016.01.003"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14129"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912217"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25396"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.5504"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2016.08.001"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1214704"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02556-08"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2017.06.010"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.015"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2146-9"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1303607110"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1310522110"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1203-9"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.20"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-16-0003"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2015.03.005"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/oncsis.2015.39"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15977"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13027-016-0068-7"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00840-12"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910560607"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2010.12.005"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djk179"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-08-0347"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1159\/000381717"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0537"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1208130"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1206923"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30735"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-015-4694-2"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.24728"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2702"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21386"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2012.11.017"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4315"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPF2XGZ2XIQYQX"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2012.08.006"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-135-35091a"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.55"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.31412","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.31412","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T18:35:27Z","timestamp":1694802927000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.31412"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,17]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1002\/ijc.31412"],"URL":"https:\/\/doi.org\/10.1002\/ijc.31412","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,17]]},"assertion":[{"value":"2017-11-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}