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To determine their likely site of origin, we combined exome sequencing from 33 <jats:styled-content style=\"fixed-case\">MUP<\/jats:styled-content>s to assess the total rate of somatic mutations and degree of <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content> mutagenesis. An independent cohort of 91 archival <jats:styled-content style=\"fixed-case\">MUP<\/jats:styled-content>s was also screened for 46 hot spot mutations highly prevalent in melanoma including <jats:italic><jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">NRAS<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">GNAQ<\/jats:styled-content><\/jats:italic>, and <jats:italic><jats:styled-content style=\"fixed-case\">GNA<\/jats:styled-content>11<\/jats:italic>. Results showed that the majority of <jats:styled-content style=\"fixed-case\">MUP<\/jats:styled-content>s exhibited high somatic mutation rates, high ratios of C&gt;T\/G&gt;A transitions, and a high rate of <jats:italic><jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content><\/jats:italic> (45 of 101, 45%) and <jats:italic><jats:styled-content style=\"fixed-case\">NRAS<\/jats:styled-content><\/jats:italic> (32 of 101, 32%) mutations, collectively indicating a mutation profile consistent with cutaneous sun\u2010exposed melanomas. These data suggest that a significant proportion of <jats:styled-content style=\"fixed-case\">MUP<\/jats:styled-content>s arise from regressed or unrecognized primary cutaneous melanomas or arise de novo in lymph nodes from nevus cells that have migrated from the skin.<\/jats:p>","DOI":"10.1111\/pcmr.12153","type":"journal-article","created":{"date-parts":[[2013,7,25]],"date-time":"2013-07-25T17:04:38Z","timestamp":1374771878000},"page":"852-860","source":"Crossref","is-referenced-by-count":60,"title":["Melanomas of unknown primary have a mutation profile consistent with cutaneous sun\u2010exposed melanoma"],"prefix":"10.1111","volume":"26","author":[{"given":"Ken","family":"Dutton\u2010Regester","sequence":"first","affiliation":[{"name":"Oncogenomics Laboratory QIMR Berghofer Medical Research Institute Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hojabr","family":"Kakavand","sequence":"additional","affiliation":[{"name":"Melanoma Institute of 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Australia (formerly the Sydney Melanoma Unit) North Sydney NSW Australia"},{"name":"Westmead Millennium Institute Westmead NSW Australia"},{"name":"The University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"Haydu","sequence":"additional","affiliation":[{"name":"Melanoma Institute of Australia (formerly the Sydney Melanoma Unit) North Sydney NSW Australia"},{"name":"The University of Sydney Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Cancer Immunotherapy Laboratory QIMR Berghofer Medical Research Institute Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham J.","family":"Mann","sequence":"additional","affiliation":[{"name":"Melanoma Institute of Australia (formerly the Sydney Melanoma Unit) North Sydney NSW Australia"},{"name":"Westmead Millennium 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