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The melanomas were excised, and as a preventive measure, the remainder of the nevi depigmentosa were removed. We performed whole\u2010exome sequencing on excised tissue from the nevus depigmentosus, adjacent normal skin, and saliva to explain this intriguing phenomenon. We also performed a GeneTrails Comprehensive Solid Tumor Panel analysis on one of the melanoma tissues. Genetic analysis revealed germline <jats:italic>MC1R<\/jats:italic> V92M and <jats:italic>TYR<\/jats:italic> R402Q polymorphisms and a <jats:italic>MET<\/jats:italic> E168D germline mutation that may have increased the risk of melanoma development. This genetic predisposition, combined with a patient\u2010reported history of substantial sun exposure and sunburns, which were more severe within the boundaries of the nevi depigmentosa due to the lack of photoprotective melanin, produced numerous somatic mutations in the melanocytes of the nevi depigmentosa. Fitting with this paradigm for melanoma development in chronically sun\u2010damaged skin, the patient's melanomas harbored somatic mutations in <jats:italic>CDKN2A<\/jats:italic> (splice site), <jats:italic>NF1<\/jats:italic>, and <jats:italic>ATRX<\/jats:italic> and had a tumor mutation burden in the 90\u201395th percentile for melanoma.<\/jats:p>","DOI":"10.1111\/pcmr.12979","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T07:46:16Z","timestamp":1619077576000},"page":"1123-1130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic analysis of multiple primary melanomas arising within the boundaries of congenital nevi depigmentosa"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3926-5455","authenticated-orcid":false,"given":"Allison M.","family":"Fuiten","sequence":"first","affiliation":[{"name":"Department of Dermatology Oregon Health 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