{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T13:40:44Z","timestamp":1793194844863,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Screening for gene mutations has become routine clinical practice across numerous tumor entities, including melanoma. <jats:italic>BAP1<\/jats:italic> gene mutations have been identified in various tumor types and acknowledged as a critical event in metastatic uveal melanoma, but their role in non-uveal melanoma remains inadequately characterized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective analysis of all melanomas sequenced in our department from 2014\u20132022 (n=2650) was conducted to identify <jats:italic>BAP1<\/jats:italic> mutated samples. Assessment of clinical and genetic characteristics was performed as well as correlations with treatment outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>BAP1<\/jats:italic> mutations were identified in 129 cases and distributed across the entire gene without any apparent hot spots. Inactivating <jats:italic>BAP1<\/jats:italic> mutations were more prevalent in uveal (55%) compared to non-uveal (17%) melanomas. Non-uveal <jats:italic>BAP1<\/jats:italic> mutated melanomas frequently exhibited UV-signature mutations and had a significantly higher mutation load than uveal melanomas. <jats:italic>GNAQ<\/jats:italic> and <jats:italic>GNA11<\/jats:italic> mutations were common in uveal melanomas, while MAP-Kinase mutations were frequent in non-uveal melanomas with <jats:italic>NF1<\/jats:italic>, <jats:italic>BRAF<\/jats:italic> V600 and <jats:italic>NRAS<\/jats:italic> Q61 mutations occurring in decreasing frequency, consistent with a strong UV association. Survival outcomes did not differ among non-uveal melanoma patients based on whether they received targeted or immune checkpoint therapy, or if their tumors harbored inactivating <jats:italic>BAP1<\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In contrast to uveal melanomas, where <jats:italic>BAP1<\/jats:italic> mutations serve as a significant prognostic indicator of an unfavorable outcome, <jats:italic>BAP1<\/jats:italic> mutations in non-uveal melanomas are primarily considered passenger mutations and do not appear to be relevant from a prognostic or therapeutic perspective.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1383125","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T06:44:31Z","timestamp":1717569871000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Clinical and genetic characteristics of BAP1-mutated 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