{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T11:58:21Z","timestamp":1764417501641,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>DNA methylation is the most widely studied mechanism of epigenetic modification, which can influence gene expression without alterations in DNA sequences. Aberrations in DNA methylation are known to play a role in carcinogenesis, and methylation profiling has enabled the identification of biomarkers of potential clinical interest for several cancers. For vulvar squamous cell carcinoma (VSCC), however, methylation profiling remains an under-studied area. We sought to identify differentially methylated genes (DMGs) in VSCC, by performing Infinium MethylationEPIC BeadChip (Illumina) array sequencing, on a set of primary VSCC (n = 18), and normal vulvar tissue from women with no history of vulvar (pre)malignancies (n = 6). Using a false-discovery rate of 0.05, beta-difference (\u0394\u03b2) of \u00b10.5, and CpG-island probes as cut-offs, 199 DMGs (195 hyper-methylated, 4 hypo-methylated) were identified for VSCC. Most of the hyper-methylated genes were found to be involved in transcription regulator activity, indicating that disruption of this process plays a vital role in VSCC development. The majority of VSCCs harbored amplifications of chromosomes 3, 8, and 9. We identified a set of DMGs in this exploratory, hypothesis-generating study, which we hope will facilitate epigenetic profiling of VSCCs. Prognostic relevance of these DMGs deserves further exploration in larger cohorts of VSCC and its precursor lesions.<\/jats:p>","DOI":"10.3390\/cancers13143580","type":"journal-article","created":{"date-parts":[[2021,7,18]],"date-time":"2021-07-18T21:16:48Z","timestamp":1626643008000},"page":"3580","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1804-5015","authenticated-orcid":false,"given":"Shatavisha","family":"Dasgupta","sequence":"first","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia C.","family":"Ewing-Graham","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sigrid M. A.","family":"Swagemakers","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands"},{"name":"Department of Clinical Bioinformatics, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-4565","authenticated-orcid":false,"given":"Thierry P. P.","family":"van den Bosch","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peggy N.","family":"Atmodimedjo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael M. P. J.","family":"Verbiest","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marit","family":"de Haan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena C.","family":"van Doorn","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"van der Spek","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands"},{"name":"Department of Clinical Bioinformatics, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Senada","family":"Koljenovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Folkert J.","family":"van Kemenade","sequence":"additional","affiliation":[{"name":"Department of Pathology, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ygyno.2020.01.029","article-title":"Trends in HPV-dependent and HPV-independent vulvar cancers: The changing face of vulvar squamous cell carcinoma","volume":"157","author":"Eva","year":"2020","journal-title":"Gynecol. 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