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| Home > Publications database > Melanoma of unknown primary shows oncogenic pattern and clinical course of sun-exposed melanoma. |
| Home > Publications database > Melanoma of unknown primary shows oncogenic pattern and clinical course of sun-exposed melanoma. |
| Journal Article | DKFZ-2026-00420 |
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2026
Oxford University Press
Oxford
Abstract: Melanoma of unknown primary accounts for up to 10% of all metastatic melanoma patients. The origin of melanoma of unknown primary is unclear, and previous studies on the clinical course in comparison to cutaneous melanoma have reported different results.The study was conducted to assess the oncogenic pattern of melanoma of unknown primaries (MUP) and compare clinical course with melanoma of known cutaneous primary (MKP).MUP patients diagnosed between 1999 and 2022 were included in this cohort study from the prospective multicentre real-word DeCOG registry ADOREG and from the tumour database of the University Hospital Essen. For comparison, consecutive MKP patients with stage III or IV disease from the skin cancer centre Essen between 1999 and 2022 were used. The median follow-up was 3.5 years. Available tumour samples were genetically analysed using next-generation sequencing. Survival outcome was compared to MKP patients adjusted for age, sex and tumour stage with Kaplan-Meier.In total, n=727 MUP and n=587 MKP patients were identified. Median age of MUP and MKP patients at first diagnosis was 62 and 63 years, respectively. More patients were male (MUP 62%, n=448, MKP 56%, n=330). At first diagnosis, 46% of MUP (n=337) patients had stage III disease. Overall survival (OS) at 48 months was 65% (95% CI 61-69) for all MUP and 68% (95%CI 64-72) for all MKP patients. Survival analyses adjusted for age, sex and tumour stage showed comparable OS rates for MUP and MKP patients.The genetic analyses among 110 MUP patients detected C>T and CC>>TT as most common nucleotide variations. Median tumour mutational burden was 5 per million bases (95% CI 4-5). Activating BRAF V600E (c.620T > A) mutations were detected in 39.1% (n=43), activating NRAS mutations in 33.6% (n=37), RAC1 P29S mutations in 6.3% (n=7) and TERT promoter mutations in 66.4% (n=73) of the analysed tumour samples. No activating KIT mutations were detected.The oncogenic pattern of MUP showed a UV signature suggesting an origin in sun-exposed localisations. OS of MUP is comparable to melanoma of known cutaneous primary.
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