Background: BRAF mutation frequencies in melanoma subtypes have clinical implications and offer pathogenetic clues. Objectives: To characterize BRAF mutation status in melanoma of unknown primary (MUP) patients, in histological melanoma subtypes and by localization of primary tumors. Methods: In 179 patients with stage IV metastatic melanoma, BRAF mutation status, histological subtype and localization of primary (except for 29 MUP patients) were analyzed. Results: BRAF mutations were found in 44.3%, of which 80.5% were BRAF V600E and 19.5% showed non-V600E BRAF mutations. BRAF mutation frequency depended on histological subtype (57.4% superficial spreading melanoma, 54.7% nodular melanoma, 11.1% mucosal melanoma, 28.6% acral lentiginous melanoma) and concerning non-V600E BRAF mutations on localization of primary. In MUP the BRAF mutation pattern resembled superficial spreading and nodular melanomas. Conclusion: BRAF mutation frequencies depend on histological subtype and localization of primary melanoma. Non-V600E BRAF mutations mostly occur in patients with primaries on ‘head and neck' as well as ‘trunk' but not on ‘extremities'.

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