{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T12:25:51Z","timestamp":1777724751101,"version":"3.51.4"},"reference-count":35,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Investigative Medicine"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:p>Epigenetic dysregulation is an important emerging hallmark of cutaneous melanoma development. The global loss of DNA methylation in gene-poor regions and transposable DNA elements of cancer cells contributes to increased genomic instability. Long interspersed element-1 (LINE-1) sequences are the most abundant repetitive sequence of the genome and can be evaluated as a surrogate marker of the global level of DNA methylation. In this work, LINE-1 methylation levels were evaluated in cutaneous melanomas and normal melanocyte primary cell cultures to investigate their possible association with both distinct clinicopathological characteristics and tumor mutational profile. A set of driver mutations frequently identified in cutaneous melanoma was assessed by sequencing (actionable mutations in BRAF, NRAS, and KIT genes, and mutations affecting the TERT promoter) or multiplex ligation-dependent probe amplification (MLPA) ( CDKN2A deletions). Pyrosequencing was performed to investigate the methylation level of LINE-1 and CDKN2A promoter sequences. The qualitative analysis showed a trend toward an association between LINE-1 hypomethylation and CDKN2A inactivation (p=0.05). In a quantitative approach, primary tumors, mainly the thicker ones (&gt;4\u2005mm), exhibited a trend toward LINE-1 hypomethylation when compared with control melanocytes. To date, this is the first study reporting in cutaneous melanomas a possible link between the dysregulation of LINE-1 methylation and the presence of driver mutations.<\/jats:p>","DOI":"10.1136\/jim-2016-000066","type":"journal-article","created":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T19:43:02Z","timestamp":1462909382000},"page":"899-904","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Line-1 Hypomethylation and Mutational Status in Cutaneous Melanomas"],"prefix":"10.1177","volume":"64","author":[{"given":"Dimitrius T","family":"Pramio","sequence":"first","affiliation":[{"name":"International Research Center, AC Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula C","family":"Pennacchi","sequence":"additional","affiliation":[{"name":"Clinical Chemistry and Toxicology Department, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvya S","family":"Maria-Engler","sequence":"additional","affiliation":[{"name":"Clinical Chemistry and Toxicology Department, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ant\u00f4nio H J F M","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, AC Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o P","family":"Duprat","sequence":"additional","affiliation":[{"name":"Skin Cancer Department, AC Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirce M","family":"Carraro","sequence":"additional","affiliation":[{"name":"International Research Center, AC Camargo Cancer Center, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana C V","family":"Krepischi","sequence":"additional","affiliation":[{"name":"Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,3,1]]},"reference":[{"key":"bibr1-jim-2016-000066","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2004.05708.x"},{"key":"bibr2-jim-2016-000066","unstructured":"Instituto Nacional do C\u00e2ncer Jos\u00e9 Alencar Gomes da Silva (INCA). 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