Clinical phenotypes of uveal melanoma in patients with germline pathogenic/likely pathogenic BAP1 variants.

Authors

Reham Abdalla, Olivia B Taylor, Joseph McElroy, Kaylee Ramsey, Lindsey Byrne, Abdelrahman M Elsayed, Colleen M Cebulla, Mohamed H Abdel-Rahman

Published in

medRxiv : the preprint server for health sciences. Jul 01, 2026. Epub Jul 01, 2026.

Abstract

Germline pathogenic or likely pathogenic variants (GPVs) in BRCA-1 Associated Protein 1 ( BAP1 ) are associated with a spectrum of tumors, including uveal melanoma (UM). Currently, UM patients with BAP1 GPVs are treated as high-risk class 2 tumors based on mostly empiric data. In the current study, we examined the clinical phenotype of a cohort of 29 UM patients with BAP1 GPVs. We also carried out a systematic review of the literature of UM patients with BAP1 GPVs. We observed that UM patients with BAP1 GPVs have significantly lower median age of diagnosis compared to median age reported in UM patients in the Surveillance, Epidemiology, and End Results Program (SEERS) database. Metastatic risk and overall survival in the UM BAP1 GPVs cohort were statistically significant from those in patients with class 1 tumors, but were comparable to those observed in UM patients with class 2 tumors. In UM BAP1 GPVs treated with radiation (n=12), no secondary cancers were observed in the field of radiation in a median 26.5 months (range, 4-119 months) follow up period. One patient experienced a separate growth of UM at a distinct location within the same eye. These data support managing UM in patients with BAP1 GPVs as aggressive class 2 tumors, following the currently established standard of care for these high-risk tumors.
A small percent of uveal melanomas is attributed to inherited (germline) pathogenic variants in the BAP1 gene. The clinical outcome of these patients is unclear. We studied clinical characteristics, secondary tumors and survival outcomes of uveal melanoma patients with germline BAP1 pathogenic variants. Uveal melanoma patients with germline BAP1 pathogenic variants were more likely to be diagnosed earlier and their survival outcomes were poorer than those with class 1 tumors, but similar to those with class 2 tumors. In patients treated with radiation, no secondary malignancies were observed but one UM patient had a separate growth of UM at distinct location within the same eye.

PMID:
42428075
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.

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