{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T14:38:39Z","timestamp":1780324719064,"version":"3.54.1"},"reference-count":41,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T00:00:00Z","timestamp":1731801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordination for the Improvement of Higher Education Personnel (CAPES)","doi-asserted-by":"publisher","award":["88887.513947\/2020-00"],"award-info":[{"award-number":["88887.513947\/2020-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aimed to verify whether germline single nucleotide variants (SNV) in CTLA-4 gene, c.-1765C&gt;T, c.-1661A&gt;G, c.-1577G&gt;A, and c.-1478G&gt;A, influence the risk, clinicopathological aspects, and survival of patients with CM, as well as its functional consequences. A total of 432 patients with CM and 504 controls were evaluated. CTLA-4 genotypes were identified by real-time polymerase chain reaction (RT-PCR) and expression of CTLA-4 by quantitative PCR (qPCR) and luciferase assay. Cell cycle, proliferation, apoptosis\/necrosis, and migration analyses were performed in SK-MEL-28 and A-375 cell lines modified to present homozygous ancestral or variant genotypes by CRISPR technique. Individuals with the CTLA-4 c.-1577 AA genotype and the combined CTLA-4 c.-1577 and c.-1478 AA + AA genotypes were at 1.60- and 3.12-fold higher risk of developing CM, respectively. The CTLA-4 c.-1577 AA genotype was seen as an independent predictor of worse event-free survival and was also associated with higher gene expression, higher cell proliferation, lower cell apoptosis, and higher cell migration. Our data present, for the first time, evidence that CTLA-4 c.-1577G&gt;A alters the risk and clinical aspects of CM treated with conventional procedures and may be used for selecting individuals for tumor prevention and patients for distinct treatment.<\/jats:p>","DOI":"10.3390\/ijms252212327","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T04:07:09Z","timestamp":1731902829000},"page":"12327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Association of Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) Genetic Variants with Risk and Outcome of Cutaneous Melanoma"],"prefix":"10.3390","volume":"25","author":[{"given":"Ana Maria Castro","family":"Ferreira","sequence":"first","affiliation":[{"name":"Laboratory of Cancer Genetics, School of Medical Sciences, State University of Campinas, Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1108-6343","authenticated-orcid":false,"given":"Juliana","family":"Carron","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Genetics, School of Medical Sciences, State University of Campinas, Campinas 13083-970, SP, Brazil"},{"name":"Department of Anesthesiology, Oncology and Radiology, School of Medical Sciences, State University of Campinas, Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4367-4414","authenticated-orcid":false,"given":"Gabriela Vilas B\u00f4as","family":"Gomez","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Genetics, School of Medical Sciences, State University of Campinas, Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0325-5514","authenticated-orcid":false,"given":"Vinicius de Lima","family":"Vazquez","sequence":"additional","affiliation":[{"name":"Melanoma and Sarcoma Surgery Department, Barretos Cancer Hospital, Barretos 14784-400, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio Vicente","family":"Serrano","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Barretos Cancer Hospital, Barretos 14784-400, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5944-0305","authenticated-orcid":false,"given":"Gustavo Jacob","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Genetics, School of Medical Sciences, State University of Campinas, Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1314-2345","authenticated-orcid":false,"given":"Carmen Silvia Passos","family":"Lima","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Genetics, School of Medical Sciences, State University of Campinas, Campinas 13083-970, SP, Brazil"},{"name":"Department of Anesthesiology, Oncology and Radiology, School of Medical Sciences, State University of Campinas, Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Caba\u00e7o, L.C., Tomas, A., Pojo, M., and Barral, D.C. 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