{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:07:00Z","timestamp":1789456020469,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,12,11]],"date-time":"2014-12-11T00:00:00Z","timestamp":1418256000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["K08CA164047"],"award-info":[{"award-number":["K08CA164047"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["5P30CA142543"],"award-info":[{"award-number":["5P30CA142543"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Propath"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cutan Pathol"],"published-print":{"date-parts":[[2015,2]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Alterations in pathways including\n \n BRAF<\/jats:styled-content>\n <\/jats:italic>\n ,\n \n CDKN2A<\/jats:styled-content>\n <\/jats:italic>\n , and\n \n TERT<\/jats:styled-content>\n <\/jats:italic>\n contribute to the development of melanoma, but the sequence in which the genetic alterations occur and their prognostic significance remains unclear. To clarify the role of these pathways, we analyzed a primary melanoma and its metastasis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Immunohistochemistry for\n BRAF\u2010V600E<\/jats:styled-content>\n , Sanger sequencing of\n \n BRAF<\/jats:styled-content>\n <\/jats:italic>\n and the\n \n TERT<\/jats:styled-content>\n <\/jats:italic>\n promoter, fluorescence\n in\u2010situ<\/jats:italic>\n hybridization, and telomere analyses were performed on a primary melanoma and its asynchronous cerebellar metastasis. Using the log\u2010rank test and Cox\u2010proportional model, the cancer genome atlas (\n TCGA<\/jats:styled-content>\n ) cohort of melanomas was analyzed for the effect of\n \n BRAF<\/jats:styled-content>\n <\/jats:italic>\n mutation and\n \n CDKN2A<\/jats:styled-content>\n <\/jats:italic>\n loss on survival.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The primary melanoma expressed mutant\n \n BRAF<\/jats:styled-content>\n <\/jats:italic>\n \u2010\n V600E<\/jats:styled-content>\n and possessed a homozygous deletion of\n \n CDKN2A<\/jats:styled-content>\n <\/jats:italic>\n . In addition to these early defects, the metastatic lesion also possessed evidence of aneuploidy and an activating mutation of the\n \n TERT<\/jats:styled-content>\n <\/jats:italic>\n promoter. In the\n TCGA<\/jats:styled-content>\n melanoma cohort, there was a non\u2010significant trend toward poor prognosis in early stage cutaneous melanoma patients with concomitant\n \n BRAF<\/jats:styled-content>\n <\/jats:italic>\n mutation and\n \n CDKN2A<\/jats:styled-content>\n <\/jats:italic>\n loss.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n \n BRAF<\/jats:styled-content>\n <\/jats:italic>\n mutation and\n \n CDKN2A<\/jats:styled-content>\n <\/jats:italic>\n loss occurred early and\n \n TERT<\/jats:styled-content>\n <\/jats:italic>\n promoter mutation later in a case of lethal metastatic melanoma. The effects of these pathways on survival warrant further investigation in early stage cutaneous melanoma patients.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cup.12444","type":"journal-article","created":{"date-parts":[[2014,11,19]],"date-time":"2014-11-19T04:39:11Z","timestamp":1416371951000},"page":"108-117","source":"Crossref","is-referenced-by-count":14,"title":["A primary melanoma and its asynchronous metastasis highlight the role of\n \n BRAF<\/scp>\n <\/i>\n ,\n \n CDKN2A<\/scp>\n <\/i>\n , and\n \n TERT<\/i>\n <\/scp>"],"prefix":"10.1111","volume":"42","author":[{"given":"Gregory A.","family":"Hosler","sequence":"first","affiliation":[{"name":"Department of Dermatology UT Southwestern Medical Center Dallas TX USA"},{"name":"ProPath Dallas TX USA"},{"name":"Department of Pathology UT Southwestern Medical Center Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Davoli","sequence":"additional","affiliation":[{"name":"Division of Genetics Brigham and Women's Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilgen","family":"Mender","sequence":"additional","affiliation":[{"name":"Department of Cell Biology UT Southwestern Medical Center Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Litzner","sequence":"additional","affiliation":[{"name":"Department of Dermatology UT Southwestern Medical Center Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaehyuk","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Yale Medical School New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payal","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Pathology UT Southwestern Medical Center Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry 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