Co-occurrence of EIF1AX, SF3B1, or BAP1 variants in uveal melanomas: A case series and review

Purpose: The purpose of this study is to present a case series of patients with co-occurrence of either BRCA1 associated protein-1 (BAP1), eukaryotic translation initiation factor 1A, X-chromosomal (EIF1AX), or splicing factor 3B subunit 1 (SF3B1) in the detection and treatment of a uveal melanoma (...

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Main Authors: Henry C. Skrehot, Amer F. Alsoudi, Amy C. Schefler
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:American Journal of Ophthalmology Case Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2451993625000805
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author Henry C. Skrehot
Amer F. Alsoudi
Amy C. Schefler
author_facet Henry C. Skrehot
Amer F. Alsoudi
Amy C. Schefler
author_sort Henry C. Skrehot
collection DOAJ
description Purpose: The purpose of this study is to present a case series of patients with co-occurrence of either BRCA1 associated protein-1 (BAP1), eukaryotic translation initiation factor 1A, X-chromosomal (EIF1AX), or splicing factor 3B subunit 1 (SF3B1) in the detection and treatment of a uveal melanoma (UM) prior to the development of metastatic disease. Observations: This is a retrospective case series of ten patients with UM demonstrating co-occurrence of either BAP1, EIF1AX, or SF3B1 variants treated at a single ocular oncology clinic by a senior ocular oncologist between 2020 and 2024. Charts were reviewed and data on medical history, demographics, tumor characteristics, genetic testing, follow up, as well as fundus photo and B-scan ocular ultrasound were collected. The average age of the patients was 58.5 years old. The mean length of follow up was 18.2 months. Four patients had guanosine nucleotide-binding protein alpha-11 (GNA11) variants and six had guanosine nucleotide-binding protein Q (GNAQ) variants. Four patients had germline BAP1 variants. Four patients had a combination of EIF1AX and BAP1 variants. Three patients had a combination of EIF1AX and SF3B1 variants. Three patients had a combination of SF3B1 and BAP1 variants. Eight UM were gene expression profile (GEP) Class 1A and two UM were GEP Class 1B. Seven UM were preferentially expressed antigen in melanoma (PRAME) negative and three UM were PRAME positive. All patients had cytologic confirmation of the diagnosis of UM: seven had cytology results of spindle cells and three had results of mixed spindle and epithelioid cells. All patients were treated with Iodine-125 (I-125) plaque brachytherapy. Conclusions and importance: We present a case series of patients with the co-occurrence of EIF1AX, SF3B1, or BAP1. With distinct genomic aberrations, transcriptional features, and clinical outcomes, EIF1AX, SF3B1, and BAP1 are thought to be mutually exclusive. The present case series demonstrates rare exceptions to this general pattern and speculates on the early molecular steps of UM which may lead to these rare mutation combinations.
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spelling doaj-art-2f03b7029f4247f192b2749eb3d529832025-08-20T03:10:32ZengElsevierAmerican Journal of Ophthalmology Case Reports2451-99362025-06-013810232710.1016/j.ajoc.2025.102327Co-occurrence of EIF1AX, SF3B1, or BAP1 variants in uveal melanomas: A case series and reviewHenry C. Skrehot0Amer F. Alsoudi1Amy C. Schefler2School of Medicine, Baylor College of Medicine, Houston, TX, USADepartment of Ophthalmology, Baylor College of Medicine, Houston, TX, USARetina Consultants of Texas, Houston, TX, USA; Blanton Eye Institute, Weill Cornell Medicine, Houston Methodist Hospital, Houston, TX, USA; Corresponding author. Retina Consultants of Texas, 4460 Bissonnet Street, Suite 200, Houston, TX, 77030, USA.Purpose: The purpose of this study is to present a case series of patients with co-occurrence of either BRCA1 associated protein-1 (BAP1), eukaryotic translation initiation factor 1A, X-chromosomal (EIF1AX), or splicing factor 3B subunit 1 (SF3B1) in the detection and treatment of a uveal melanoma (UM) prior to the development of metastatic disease. Observations: This is a retrospective case series of ten patients with UM demonstrating co-occurrence of either BAP1, EIF1AX, or SF3B1 variants treated at a single ocular oncology clinic by a senior ocular oncologist between 2020 and 2024. Charts were reviewed and data on medical history, demographics, tumor characteristics, genetic testing, follow up, as well as fundus photo and B-scan ocular ultrasound were collected. The average age of the patients was 58.5 years old. The mean length of follow up was 18.2 months. Four patients had guanosine nucleotide-binding protein alpha-11 (GNA11) variants and six had guanosine nucleotide-binding protein Q (GNAQ) variants. Four patients had germline BAP1 variants. Four patients had a combination of EIF1AX and BAP1 variants. Three patients had a combination of EIF1AX and SF3B1 variants. Three patients had a combination of SF3B1 and BAP1 variants. Eight UM were gene expression profile (GEP) Class 1A and two UM were GEP Class 1B. Seven UM were preferentially expressed antigen in melanoma (PRAME) negative and three UM were PRAME positive. All patients had cytologic confirmation of the diagnosis of UM: seven had cytology results of spindle cells and three had results of mixed spindle and epithelioid cells. All patients were treated with Iodine-125 (I-125) plaque brachytherapy. Conclusions and importance: We present a case series of patients with the co-occurrence of EIF1AX, SF3B1, or BAP1. With distinct genomic aberrations, transcriptional features, and clinical outcomes, EIF1AX, SF3B1, and BAP1 are thought to be mutually exclusive. The present case series demonstrates rare exceptions to this general pattern and speculates on the early molecular steps of UM which may lead to these rare mutation combinations.http://www.sciencedirect.com/science/article/pii/S2451993625000805BRCA1 associated protein-1 (BAP1)Eukaryotic translation initiation factor 1AX-chromosomal (EIF1AX)Next generation sequencing (NGS)Preferentially expressed antigen in melanoma (PRAME)Splicing factor 3B subunit 1 (SF3B1)
spellingShingle Henry C. Skrehot
Amer F. Alsoudi
Amy C. Schefler
Co-occurrence of EIF1AX, SF3B1, or BAP1 variants in uveal melanomas: A case series and review
American Journal of Ophthalmology Case Reports
BRCA1 associated protein-1 (BAP1)
Eukaryotic translation initiation factor 1A
X-chromosomal (EIF1AX)
Next generation sequencing (NGS)
Preferentially expressed antigen in melanoma (PRAME)
Splicing factor 3B subunit 1 (SF3B1)
title Co-occurrence of EIF1AX, SF3B1, or BAP1 variants in uveal melanomas: A case series and review
title_full Co-occurrence of EIF1AX, SF3B1, or BAP1 variants in uveal melanomas: A case series and review
title_fullStr Co-occurrence of EIF1AX, SF3B1, or BAP1 variants in uveal melanomas: A case series and review
title_full_unstemmed Co-occurrence of EIF1AX, SF3B1, or BAP1 variants in uveal melanomas: A case series and review
title_short Co-occurrence of EIF1AX, SF3B1, or BAP1 variants in uveal melanomas: A case series and review
title_sort co occurrence of eif1ax sf3b1 or bap1 variants in uveal melanomas a case series and review
topic BRCA1 associated protein-1 (BAP1)
Eukaryotic translation initiation factor 1A
X-chromosomal (EIF1AX)
Next generation sequencing (NGS)
Preferentially expressed antigen in melanoma (PRAME)
Splicing factor 3B subunit 1 (SF3B1)
url http://www.sciencedirect.com/science/article/pii/S2451993625000805
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AT amycschefler cooccurrenceofeif1axsf3b1orbap1variantsinuvealmelanomasacaseseriesandreview