{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:11:00Z","timestamp":1790431860504,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,12,27]],"date-time":"2016-12-27T00:00:00Z","timestamp":1482796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2017,4,15]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Optimal treatments for vulvar and vaginal melanomas (VVMs) have not been identified. Herein, the authors compare molecular profiles between VVM and nongynecologic melanoma (NGM) subtypes with the objective of identifying novel, targetable biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>In total, 2304 samples of malignant melanoma that were submitted to Caris Life Sciences between 2009 and 2015 were reviewed. In situ hybridization and immunohistochemistry were used to assess copy numbers and protein expression of selected genes. Sequenced variants were analyzed using a proprietary cancer panel.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In total, 51 VVMs (14 vaginal and 37 vulvar melanomas) were compared with 2253 malignant NGMs, including 2127 cutaneous, 105 mucosal, and 21 acral melanomas. In VVMs, B\u2010Raf proto\u2010oncogene serine\/threonine kinase (<jats:italic>BRAF<\/jats:italic>) was the most frequently mutated gene (26%) compared with 8.3% of mucosal NGMs (<jats:italic>P<\/jats:italic>\u2009=\u2009.008). In <jats:italic>BRAF<\/jats:italic>\u2010mutated tumors, fewer VVMs (50%), compared with NGMs (82.1%), had a variant within the valine codon 600 (V600) domain. The <jats:italic>KIT<\/jats:italic> mutation rate was highest in VVMs (22%) compared with 3% in cutaneous (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001) and 8.8% in mucosal (<jats:italic>P<\/jats:italic>\u2009=\u2009.05) melanoma subtypes. <jats:italic>NRAS<\/jats:italic> mutations were rare in VVMs compared with cutaneous (25.9%; <jats:italic>P<\/jats:italic>\u2009=\u2009.009) and acral (40.6%; <jats:italic>P<\/jats:italic>\u2009=\u2009.002) melanoma subtypes. PD\u2010L1 (56%) and PD\u20101 (75%) were frequently expressed in VVM, whereas PI3KCA pathway mutations and estrogen receptor\/progesterone receptor expression were rare. Compared with VVMs that had KIT mutations, wild\u2010type KIT VVMs were more likely to express molecular markers suggestive of platinum resistance (ERCC1), alkylating sensitivity (MGMT), and anthracycline sensitivity (TOP2A).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The unique molecular features of VVM render this disease a distinct subtype of melanoma. Gene\u2010based molecular therapy and immunotherapies may be promising and should be evaluated in clinical trials. <jats:bold><jats:italic>Cancer<\/jats:italic> 2017;123:1333\u20131344.<\/jats:bold> \u00a9 <jats:italic>2016 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.30473","type":"journal-article","created":{"date-parts":[[2016,12,27]],"date-time":"2016-12-27T09:58:21Z","timestamp":1482832701000},"page":"1333-1344","source":"Crossref","is-referenced-by-count":120,"title":["Vulvar and vaginal melanoma: A unique subclass of mucosal melanoma based on a comprehensive molecular analysis of 51 cases compared with 2253 cases of nongynecologic melanoma"],"prefix":"10.1002","volume":"123","author":[{"given":"June Y.","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology and Herbert Irving Comprehensive Cancer Center Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Baptiste","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Herbert Irving Comprehensive Cancer Center Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhika Bangalore","family":"Hombalegowda","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Herbert Irving Comprehensive Cancer Center Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana I.","family":"Tergas","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Herbert Irving Comprehensive Cancer Center Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital New York New York"},{"name":"Department of Epidemiology Mailman School of Public Health, Columbia University New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Feldman","sequence":"additional","affiliation":[{"name":"Medical Affairs Department Caris Life Sciences Phoenix Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3871-4282","authenticated-orcid":false,"given":"Nathaniel L.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Herbert Irving Comprehensive Cancer Center Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeshna","family":"Chatterjee\u2010Paer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Herbert Irving Comprehensive Cancer Center Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ama","family":"Bus\u2010Kwolfski","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Herbert Irving Comprehensive Cancer Center Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D.","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Herbert Irving Comprehensive Cancer Center Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Burke","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Herbert Irving Comprehensive Cancer 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