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We therefore performed whole\u2010exome sequencing (WES) on 19 matched OMM tumor\/normal pairs in order to gain insight into potential genetic drivers of tumor formation. For the first time, we describe the comprehensive mutational profile of OMM. Our data suggest that the genetic background of OMM differs from those of other melanoma subtypes. We identified recurrent mutations involving <jats:italic>KIT<\/jats:italic>, <jats:italic>POLE<\/jats:italic>, <jats:italic>PTPRD<\/jats:italic>, <jats:italic>PTCHD2<\/jats:italic>, and <jats:italic>DMXL2<\/jats:italic>. Notably, copy number analysis revealed recurrently amplified regions of 12q14 (57.9%, containing <jats:italic>CDK4<\/jats:italic>) and 5p15 (47.4%, containing <jats:italic>TERT<\/jats:italic>). CNV analysis in a separate cohort of 15 samples validated the frequent CNV in <jats:italic>CDK4<\/jats:italic> and <jats:italic>TERT<\/jats:italic>. We also observed that the melanocyte development and pigmentation signaling pathway is frequently altered in OMM. Furthermore, our data suggest several altered genes that may be amenable for targeted therapy. We identified one patient with metastatic OMM in our cohort who was identified to harbor a targetable <jats:italic>KIT<\/jats:italic> mutation using our WES results. This patient was able to achieve complete remission following implementation of <jats:italic>KIT<\/jats:italic>\u2010targeted therapy. These findings provide further insight into the genetic underpinnings of OMM development and suggest that patients with OMM may benefit from WES analysis to identify potential targetable genetic mutations. Copyright \u00a9 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.5017","type":"journal-article","created":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T04:39:08Z","timestamp":1513053548000},"page":"358-366","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Whole\u2010exome sequencing of oral mucosal melanoma reveals mutational profile and therapeutic targets"],"prefix":"10.1002","volume":"244","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6280-8687","authenticated-orcid":false,"given":"Jiong","family":"Lyu","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial\u2010Head and Neck Oncology, Ninth People's Hospital Shanghai Jiaotong University School of Medicine  Shanghai PR China"},{"name":"Department of Stomatology First Affiliated Hospital of Zhejiang University  Hangzhou PR 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