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Multigene Panel Testing Outcomes in Patients with Uveal Melanoma: Implementation of National Guidelines

Byrne, L.; Gray, I.; Ramsey, K.; McElroy, J.; Schreiner, E.; Wolfe, J.; Taylor, O. B.; Davidorf, F.; Cebulla, C. M.; Abdel-Rahman, M. H.

2025-12-04 ophthalmology
10.64898/2025.11.26.25341005 medRxiv
Show abstract

This study aimed to evaluate the outcome of germline clinical genetic testing in uveal melanoma (UM) patients who met the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing. A retrospective chart review was conducted on UM patients seen in The Ohio State University Cancer Genetics Clinic between 5/1/2021-9/19/2025. Seventy individuals underwent clinical genetic testing, primarily via large multi-gene panels. Ten UM patients, including two related individuals, had pathogenic or likely pathogenic (P/LP) variants in known cancer genes (BAP1, BRCA1, BRCA2, MBD4, MUTYH, POT1, XRCC2). Among unrelated individuals, the positive rate was12.9% (8/70). Excluding carrier genes, the rate was10% (7/70) Eight patients would have been missed if only tested for BAP1 per ASCO 2024 recommendations. There was no association between tumor size, stage and germline P/LP variants. In summary, NCCN guidelines are useful in the prioritization of UM patients for genetic testing. Additionally, large panel testing, rather than BAP1 single gene testing, is recommended.

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