{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T19:42:14Z","timestamp":1785786134074,"version":"3.56.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"EORTC Melanoma Group"},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["RTG 2535"],"award-info":[{"award-number":["RTG 2535"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Melanoma of unknown primary (MUP) accounts for up to 10% of all cases of metastatic melanoma. The origin of MUP is unclear, and previous studies on the clinical course in comparison with cutaneous melanoma have reported varying results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The study was conducted to assess the oncogenic pattern of MUP and to compare the clinical course with that of melanoma of known cutaneous primary (MKP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with MUP diagnosed between 1999 and 2022 were included in this cohort study from the prospective multicentre real-world DeCOG (German Dermatologic Cooperative Oncology Group) registry ADOREG and from the tumour database of the University Hospital Essen. For comparison, a cohort of consecutive patients with MKP with stage III or IV disease from the skin cancer centre Essen between 1999 and 2022 was used. The median follow-up was 3.5\u2005years. Available tumour samples were genetically analysed using next-generation sequencing. Survival outcome adjusted for age, sex and tumour stage was compared between patients with MUP and those with MKP, using the Kaplan\u2013Meier method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 727 patients with MUP and 587 with MKP were identified. Median age at first diagnosis was 62\u2005years [interquartile range (IQR) 53\u201373] for MUP and 63\u2005years (IQR 52\u201375) for MKP. Most patients were male, 448 (61.6%) with MUP and 330 (56.2%) with MKP. Of the 727 patients with MUP, 337 (46.4%) had stage III disease at first diagnosis. Overall survival (OS) at 48\u2005months was 65% [95% confidence interval (CI) 61\u201369] for all patients with MUP and 68% (95% CI 64\u201372) for all patients with MKP. Survival analyses adjusted for age, sex and tumour stage showed comparable OS rates for patients with MUP and MKP. Genetic analyses of tumours from 110 patients with MUP detected C&amp;gt;T and CC\u2192TT mutations as the most common nucleotide variations. Median tumour mutational burden was 5 mutations per Mb (95% CI 4\u20135). Activating BRAF V600E (c.620T&amp;gt;A) mutations were detected in 43 patients (39.1%), activating NRAS mutations in 37 (33.6%), RAC1 P29S mutations in 7 (6.3%) and TERT promoter mutations in 73 (66.4%) of the analysed tumour samples. No activating KIT mutations were detected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The oncogenic pattern of MUP showed an ultraviolet mutation signature, suggesting an origin in sun-exposed areas. OS of MUP is comparable with that of MKP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjd\/ljaf499","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T12:56:43Z","timestamp":1765025803000},"page":"843-853","source":"Crossref","is-referenced-by-count":2,"title":["Melanoma of unknown primary shows an oncogenic pattern and clinical course of sun-exposed melanoma"],"prefix":"10.1093","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6930-2694","authenticated-orcid":false,"given":"Georg","family":"Lodde","sequence":"first","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital Essen , Essen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonida","family":"Dollani","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital Essen , Essen 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the University Cancer Centre Dresden and National Centre for Tumour Diseases , Dresden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Gutzmer","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Johannes Wesling Medical Centre Minden, Ruhr University Bochum , Minden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9060-4961","authenticated-orcid":false,"given":"Michael","family":"Weichenthal","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel , Kiel ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5316-0241","authenticated-orcid":false,"given":"Jochen","family":"Utikal","sequence":"additional","affiliation":[{"name":"Skin Cancer Unit, German Cancer Research Centre (DKFZ) , Heidelberg ,","place":["Germany"]},{"name":"Department of Dermatology, Venerology, and Allergology, University Medical Centre Mannheim, Ruprecht-Karl University of Heidelberg , Mannheim ,","place":["Germany"]},{"name":"DKFZ Hector Cancer Institute at the University Medical Centre Mannheim , Mannheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4238-9486","authenticated-orcid":false,"given":"Rudolf","family":"Herbst","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Helios Klinikum Erfurt , Erfurt ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8019-1577","authenticated-orcid":false,"given":"Ulrike","family":"Leiter","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Tuebingen , Tuebingen 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