Characterization of somatic mutations in sporadic uveal melanoma and uveal melanoma in patients with germline BAP1 pathogenic variants.

Genetic analyses were conducted on tumor samples from 88 patients with uveal melanoma (UM), 6 of whom carry pathogenic germline variants in BAP1. We assessed the frequency, pattern, and prognostic significance of somatic aberrations, and investigated differences between germline BAP1 variant carriers compared to sporadic cases. The frequency of the main oncogenic driver mutations was not significantly different between these groups. Patients with germline BAP1 variants did not have significantly different overall survival compared to the wildtype or somatic BAP1 mutation groups. Patients with a somatic BAP1 mutation (n = 24) had a significantly worse prognosis compared to wildtype (n = 58). All patients with stage III tumors and a somatic BAP1 mutation (n = 7) developed metastasis, however four of 28 stage I-II tumors without metastasis had somatic BAP1 mutations, with observation time >5 years. The tumor from one germline BAP1 carrier (stage IIIC) with a somatic EIF1AX splice variant, has not developed metastasis within a 22-year observation time.

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Copyright: © 2024 Wadt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

KSR reports having received personal fees from Bayer and Amgen and paid travel and accommodation expenses from Roche and Bristol-Myers Squibb. Besides this KRS reports having received research grants for his institution from the following: Lilly, Roche/Genentech, Bristol-Myers Squibb, Symphogen, Pfzer, Novartis, Loxo, Bayer, Alligator Bioscience, Incyte, Cantargia AB, Genmab, Puma Biotechnology, Orion Clinical, Monta BioScience, and Bioinvent. Karin Anna Wallentin Wadt reports having received personal fees from Seagen Denmark ApS, Danmark, to give a lecture. This does not alter our adherence to PLOS ONE policies on sharing data and materials.