{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:19:47Z","timestamp":1760059187095,"version":"build-2065373602"},"reference-count":24,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnlogia (FCT)","doi-asserted-by":"publisher","award":["CAC\/0007\/2022"],"award-info":[{"award-number":["CAC\/0007\/2022"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chcelldiagnostics Ltd.","award":["CAC\/0007\/2022"],"award-info":[{"award-number":["CAC\/0007\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Background\/Objectives: The methylation of the hypermethylated oncological region (THOR) of human telomerase reverse transcriptase (hTERT) may forecast tumour aggressiveness. This pilot study aimed to evaluate THOR methylation as a potential biomarker for recurrence\/malignant transformation in salivary gland pleomorphic adenomas (PA). Methods: THOR methylation was assessed by quantitative pyrosequencing in 96 parotid tissue samples (benign and malignant), including non-neoplastic parotid tissue, PA, recurrent PA (rPA), and carcinomas, along with their adjacent tissues. TERT promoter mutations (TPMs) were analysed by Sanger sequencing. Results: THOR methylation significantly differed across the seven groups. Malignant tissues showed higher THOR methylation than non-neoplastic tissues, whereas benign tumours showed no significant difference from non-neoplastic tissue. THOR methylation in rPA was closer to carcinoma than to normal tissue, similar in rPA and tissues adjacent to rPA, and higher in tissues adjacent to carcinomas than in non-neoplastic tissues. A subset of PA-adjacent tissues showed epigenetic alterations, suggesting an increased risk of recurrence or malignant transformation (5\u201315%). No TPMs were detected. Conclusions: THOR methylation may add information to differentiate normal from carcinogenic tissues and, as such, may be included in a biomarkers panel. Epigenetic alterations in PA-adjacent tissues with normal histology highlight the need for improved diagnostic markers.<\/jats:p>","DOI":"10.3390\/curroncol32060312","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T06:30:26Z","timestamp":1748413826000},"page":"312","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Methylation Status of the Telomerase Reverse Transcriptase Promoter in Parotid Tumours and Adjacent Parotid Gland Tissue: A Pilot Study on the Implications for Recurrence and Development of Malignancy"],"prefix":"10.3390","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8725-0202","authenticated-orcid":false,"given":"Ant\u00f3nio","family":"Paiva-Correia","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal"},{"name":"Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, Gambelas Campus, 8005-139 Faro, Portugal"},{"name":"Cellular Pathology Department, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester M23 9LT, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9727-1813","authenticated-orcid":false,"given":"Joana","family":"Apol\u00f3nio","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal"},{"name":"Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, Gambelas Campus, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5366-093X","authenticated-orcid":false,"given":"Alfons","family":"Nadal","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Clinic, 08036 Barcelona, Spain"},{"name":"Department of Basic Clinical Practice, School of Medicine, University of Barcelona, 08007 Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5861-5409","authenticated-orcid":false,"given":"Jos\u00e9 Ricardo","family":"Brand\u00e3o","sequence":"additional","affiliation":[{"name":"Unidade local de Saude de Santo Antonio, 4099-001 Porto, Portugal"},{"name":"Unilabs, Avenida de Fran\u00e7a, 434, 4050-277 Porto, Portugal"}]},{"given":"N\u00e1dia","family":"Silva","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal"},{"name":"Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, Gambelas Campus, 8005-139 Faro, Portugal"}]},{"given":"Bianca","family":"Machado","sequence":"additional","affiliation":[{"name":"Instituto Portugu\u00eas de Oncologia do Porto (IPO-Porto), Anatomia Patologica, 4100-321 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2142-0608","authenticated-orcid":false,"given":"Ivan","family":"Archilla","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Clinic, 08036 Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3453-3978","authenticated-orcid":false,"given":"Pedro","family":"Castelo-Branco","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal"},{"name":"Cellular Pathology Department, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester M23 9LT, UK"},{"name":"Champalimaud Research Program, Champalimaud Centre for the Unknown, 1400-038 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9998-8212","authenticated-orcid":false,"given":"Henrik","family":"Hellquist","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, Gambelas Campus, Bld. 2, 8005-139 Faro, Portugal"},{"name":"Algarve Biomedical Center Research Institute (ABC-RI), University of Algarve, Gambelas Campus, 8005-139 Faro, Portugal"},{"name":"Department of Cellular Pathology, Northern Lincolnshire and Goole NHS Foundation Trust, Lincoln 999039, UK"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0022-2836(78)90294-2","article-title":"A tandemly repeated sequence at the termini of the extrachromossomal ribosomal RNA in Tetrahymena","volume":"120","author":"Blackburn","year":"1978","journal-title":"J. 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