{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:54:34Z","timestamp":1791438874711,"version":"4.3.3"},"reference-count":22,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021201","name":"European Academy of Dermatology and Venereology","doi-asserted-by":"publisher","award":["PPRC\u20102018\u201036"],"award-info":[{"award-number":["PPRC\u20102018\u201036"]}],"id":[{"id":"10.13039\/501100021201","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Dermatology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n The use of targeted therapies, such as\n BRAF\/MEK<\/jats:italic>\n inhibitors, has led to a considerable increase in melanoma\u2010specific survival rates; however, prolonged responses remain uneven and uncertain. Moreover, there is a lack of reliable biomarkers that can predict the type and duration of the response. This study aimed to determine whether\n pTERT<\/jats:italic>\n mutations affect progression\u2010free survival and overall survival in melanoma patients treated with\n BRAF\/MEK<\/jats:italic>\n inhibitors.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n \n This study employed a retrospective observational design. We included 77 patients with metastatic\n BRAF<\/jats:italic>\n (V600) mutated melanoma treated with BRAF\/MEK inhibitors. The data analysis included only patients with known\n p<\/jats:italic>\n TERT<\/jats:italic>\n mutation status (WT, \u2212124C>T, \u2212146C>T, and \u2212138_139 CC>TT) and clinical variables collected at two different centers. Progression\u2010free survival and overall survival were determined using Kaplan\u2013Meier curves and Cox regression models.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A multivariate analysis with 56\u2010month follow\u2010up suggested a decreased melanoma overall survival with\n BRAF<\/jats:italic>\n (\n V600K<\/jats:italic>\n ) mutation (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.2\u20134.0;\n p<\/jats:italic>\n \u2009=\u20090.016), the Stage M1c\/M1d (HR 3.3; 95% CI 1.7\u20136.5;\n p<\/jats:italic>\n \u2009=\u20090.001), ECOG \u2265\u20091 (HR 3.6; 95% CI 1.9\u20136.7;\n p<\/jats:italic>\n \u2009=\u20090.001) and not having the \u2212138_139 CC>TT p\n TERT<\/jats:italic>\n mutation (HR 3.2; 95% CI 1.0\u201310.5;\n p<\/jats:italic>\n \u2009=\u20090.052).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These findings suggest that the tandem \u2212138_139 CC>TT, a less frequent\n p<\/jats:italic>\n TERT<\/jats:italic>\n mutation subtype, may be associated with a trend toward improved prognosis in patients with metastatic melanoma treated with\n BRAF\/MEK<\/jats:italic>\n inhibitors. However, due to the limited sample size, this study is essentially an exploratory investigation. It requires independent validation with a larger sample to determine the effect of\n TERT<\/jats:italic>\n promoter mutations, together with other clinical parameters, on treatment response to\n BRAF\/MEK<\/jats:italic>\n inhibitors.\n <\/jats:p>\n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ijd.70553","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:19:48Z","timestamp":1783484388000},"page":"2315-2322","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association Between\n pTERT<\/scp>\n Promoter Mutation Subtypes and Survival Outcomes in\n BRAF<\/scp>\n \u2010Mutant Metastatic Melanoma Treated With\n BRAF<\/scp>\n \/\n MEK<\/scp>\n Inhibitors: An Exploratory Study"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2972-7222","authenticated-orcid":false,"given":"Esperanza","family":"Manrique\u2010Silva","sequence":"first","affiliation":[{"name":"Escuela de Doctorado Universidad Cat\u00f3lica de Valencia \u201cSan Vicente M\u00e1rtir\u201d Val\u00e8ncia Spain"},{"name":"Department of Dermatology Fundaci\u00f3n Instituto Valenciano de Oncolog\u00eda Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maider","family":"Aguerralde\u2010Martin","sequence":"additional","affiliation":[{"name":"Department of Applied Statistics, Operational Research and Quality Universitat Polit\u00e8cnica de Val\u00e8ncia Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaida","family":"Garc\u00eda\u2010Casado","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology Fundaci\u00f3n Instituto Valenciano de Oncolog\u00eda Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mill\u00e1n\u2010Esteban","sequence":"additional","affiliation":[{"name":"School of Medicine Universidad Cat\u00f3lica de Valencia \u201cSan Vicente M\u00e1rtir\u201d Val\u00e8ncia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4837-4998","authenticated-orcid":false,"given":"Ruggero","family":"Moro","sequence":"additional","affiliation":[{"name":"Department of Dermatology Fundaci\u00f3n Instituto Valenciano de Oncolog\u00eda Valencia Spain"},{"name":"Instituto Dermatol\u00f3gico Dr. Alonso, Hospital Vithas Valencia 9 de Octubre Valencia Espa\u00f1a"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Requena","sequence":"additional","affiliation":[{"name":"Department of Dermatology Fundaci\u00f3n Instituto Valenciano de Oncolog\u00eda Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Trav\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy Fundaci\u00f3n Instituto Valenciano de Oncolog\u00eda Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaya","family":"Vir\u00f3s","sequence":"additional","affiliation":[{"name":"Skin Cancer and Aging Lab, Cancer Research UK Manchester Institute University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0098-1406","authenticated-orcid":false,"given":"Simone","family":"Ribero","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Dermatology Clinic University of Turin Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6093-0395","authenticated-orcid":false,"given":"Rajiv","family":"Kumar","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Informatics University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Nagore","sequence":"additional","affiliation":[{"name":"Escuela de Doctorado Universidad Cat\u00f3lica de Valencia \u201cSan Vicente M\u00e1rtir\u201d Val\u00e8ncia Spain"},{"name":"Department of Dermatology Fundaci\u00f3n Instituto Valenciano de Oncolog\u00eda Valencia Spain"},{"name":"School of Medicine Universidad Cat\u00f3lica de Valencia \u201cSan Vicente M\u00e1rtir\u201d Val\u00e8ncia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12082224"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103684"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12441"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1230062"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4401"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2013.11.005"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03033-1"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33750"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2016.11.002"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.19297"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.11.009"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","unstructured":"J. J.Andres\u2010Lencina S.Rachakonda Z.Garcia\u2010Casado et\u00a0al. \u201cTERT Promoter Mutation Subtypes and Survival in Stage I and II Melanoma Patients \u201d2018.","DOI":"10.1002\/ijc.31780"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2021.103288"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.13155"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao0535"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2018-205653"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3240"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15112888"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2004707117"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.26688"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2019.06.149"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12040946"}],"container-title":["International Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ijd.70553","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ijd.70553","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ijd.70553","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:33:17Z","timestamp":1791437597000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ijd.70553"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":22,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1111\/ijd.70553"],"URL":"https:\/\/doi.org\/10.1111\/ijd.70553","archive":["Portico"],"relation":{},"ISSN":["0011-9059","1365-4632"],"issn-type":[{"value":"0011-9059","type":"print"},{"value":"1365-4632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"assertion":[{"value":"2026-03-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}