{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:21:37Z","timestamp":1792092097744,"version":"4.4.0"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2014\/50943-1"],"award-info":[{"award-number":["2014\/50943-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["465682\/2014-6"],"award-info":[{"award-number":["465682\/2014-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88887.136405\/2017-00"],"award-info":[{"award-number":["88887.136405\/2017-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Genetic predisposition accounts for nearly 10% of all melanoma cases and has been associated with a dozen moderate- to high-penetrance genes, including <jats:italic>CDKN2A<\/jats:italic>, <jats:italic>CDK4<\/jats:italic>, <jats:italic>POT1<\/jats:italic> and <jats:italic>BAP1<\/jats:italic>. However, in most melanoma-prone families, the genetic etiology of cancer predisposition remains undetermined. The goal of this study was to identify rare genomic variants associated with cutaneous melanoma susceptibility in melanoma-prone families. Whole-exome sequencing was performed in 2 affected individuals of 5 melanoma-prone families negative for mutations in <jats:italic>CDKN2A<\/jats:italic> and <jats:italic>CDK4<\/jats:italic>, the major cutaneous melanoma risk genes. A total of 288 rare coding variants shared by the affected relatives of each family were identified, including 7 loss-of-function variants. By performing <jats:italic>in silico<\/jats:italic> analyses of gene function, biological pathways, and variant pathogenicity prediction, we underscored the putative role of several genes for melanoma risk, including previously described genes such as <jats:italic>MYO7A<\/jats:italic> and <jats:italic>WRN<\/jats:italic>, as well as new putative candidates, such as <jats:italic>SERPINB4<\/jats:italic>, <jats:italic>HRNR<\/jats:italic>, and <jats:italic>NOP10<\/jats:italic>. In conclusion, our data revealed rare germline variants in melanoma-prone families contributing with a novel set of potential candidate genes to be further investigated in future studies.<\/jats:p>","DOI":"10.1371\/journal.pone.0262419","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T18:32:30Z","timestamp":1643308350000},"page":"e0262419","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Family-based whole-exome sequencing identifies rare variants potentially related to cutaneous melanoma predisposition in Brazilian melanoma-prone families"],"prefix":"10.1371","volume":"17","author":[{"given":"Felipe","family":"Fidalgo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8659-5329","authenticated-orcid":true,"given":"Giovana 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