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Uveal melanoma is the most common primary cancer of the eye and often results in fatal metastasis. Here, we describe mutations occurring exclusively at codon 625 of the SF3B1 gene, encoding splicing factor 3B subunit 1, in low-grade uveal melanomas with good prognosis. Thus, uveal melanoma is among a small group of cancers associated with SF3B1 mutations, and these mutations denote a distinct molecular subset of uveal melanomas.
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http://dx.doi.org/10.1038/ng.2523 | DOI Listing |
Cureus
August 2025
Department of Ophthalmology, Hôpital Maisonneuve-Rosemont, Montreal, CAN.
Choroidal metastasis from occult cutaneous melanoma is rare and can masquerade as ocular inflammation. A 70‑year‑old man with sectoral anterior scleritis was found on multimodal imaging to have a solitary choroidal mass with mild periscleral fluid, prompting systemic evaluation that uncovered colonic polyps that, on histopathology, contained metastatic melanoma, a scalp primary, and widespread visceral, nodal, and intracranial metastases. Tumour cells stained HMB‑45, Melan‑A, and SOX10 positive, AE1/AE3 negative, and carried an NRAS‑Q61 mutation with wild‑type BRAF, confirming cutaneous origin.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
September 2025
Department of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany.
Purpose: Tebentafusp has emerged as the first systemic therapy to significantly prolong survival in treatment-naïve HLA-A*02:01 + patients with unresectable or metastatic uveal melanoma (mUM). Notably, a survival benefit has been observed even in the absence of radiographic response. This study aims to investigate the feasibility and prognostic value of artificial intelligence (AI)-assisted quantification and metabolic response assessment of [F]FDG long axial field-of-view (LAFOV) PET/CT in mUM patients undergoing tebentafusp therapy.
View Article and Find Full Text PDFRare melanoma subtypes, including acral, mucosal, and uveal melanomas, exhibit limited responses to immune checkpoint inhibitors (ICIs), yet the molecular mechanisms of immune resistance remain poorly defined. Here, we performed transcriptomic profiling of patient-derived xenografts (PDXs) and publicly available tumor datasets to systematically compare intratumoral gene expression across cutaneous and rare melanoma subtypes. We identified a convergent downregulation of innate immune pathogen sensing (IIPS) and type I interferon signaling pathways in rare melanomas compared to cutaneous, with lower expression also observed in anti-PD-1 non-responder tumors.
View Article and Find Full Text PDFOphthalmol Retina
September 2025
Ophthalmology Division, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Ophthalmol Retina
September 2025
Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa; University of Iowa, Institute for Vision Research, Iowa City, Iowa.