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- Title
Clinical and genetic characteristics of BAP1-mutated non-uveal and uveal melanoma.
- Authors
Matull, Johanna; Placke, Jan-Malte; Lodde, Georg; Zaremba, Anne; Utikal, Jochen; Terheyden, Patrick; Pföhler, Claudia; Herbst, Rudolf; Kreuter, Alexander; Welzel, Julia; Kretz, Julia; Möller, Inga; Sucker, Antje; Paschen, Annette; Livingstone, Elisabeth; Zimmer, Lisa; Hadaschik, Eva; Ugurel, Selma; Schadendorf, Dirk; Thielmann, Carl Maximilian
- Abstract
Background: Screening for gene mutations has become routine clinical practice across numerous tumor entities, including melanoma. BAP1 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. Methods: A retrospective analysis of all melanomas sequenced in our department from 2014-2022 (n=2650) was conducted to identify BAP1 mutated samples. Assessment of clinical and genetic characteristics was performed as well as correlations with treatment outcome. Results: BAP1 mutations were identified in 129 cases and distributed across the entire gene without any apparent hot spots. Inactivating BAP1 mutations were more prevalent in uveal (55%) compared to non-uveal (17%) melanomas. Nonuveal BAP1 mutated melanomas frequently exhibited UV-signature mutations and had a significantly higher mutation load than uveal melanomas. GNAQ and GNA11 mutations were common in uveal melanomas, while MAP-Kinase mutations were frequent in non-uveal melanomas with NF1, BRAF V600 and NRAS 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 BAP1 mutations. Conclusion: In contrast to uveal melanomas, where BAP1 mutations serve as a significant prognostic indicator of an unfavorable outcome, BAP1 mutations in non-uveal melanomas are primarily considered passenger mutations and do not appear to be relevant from a prognostic or therapeutic perspective.
- Subjects
UVEA cancer; BRAF genes; MELANOMA; IMMUNE checkpoint proteins; SURVIVAL rate; GENETIC mutation; MEDICAL screening
- Publication
Frontiers in Immunology, 2024, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2024.1383125