Pathogenic Germline Variants in Uveal Melanoma Driver and BAP1-Associated Genes in Finnish Patients with Uveal Melanoma.

Autor: Repo PE; Eye Genetics Group, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland.; Ocular Oncology Service, Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Jakkula E; Department of Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Hiltunen J; Eye Genetics Group, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland., Putkuri H; Eye Genetics Group, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland., Staskiewicz-Tuikkanen A; Eye Genetics Group, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland., Järvinen RS; Eye Genetics Group, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland., Täll M; Ocular Oncology Service, Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Raivio V; Ocular Oncology Service, Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Al-Jamal RT; Ocular Oncology Service, Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Kivelä TT; Ocular Oncology Service, Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Turunen JA; Eye Genetics Group, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland.; Ophthalmic Genetics and Rare eye Diseases Service, Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Jazyk: angličtina
Zdroj: Pigment cell & melanoma research [Pigment Cell Melanoma Res] 2025 Jan; Vol. 38 (1), pp. e13198. Date of Electronic Publication: 2024 Sep 30.
DOI: 10.1111/pcmr.13198
Abstrakt: Uveal melanoma (UM) is a rare yet aggressive eye cancer causing over 50% mortality from metastasis. Familial UM, amounting to 1%-6% of patients in Finland and the United States, mostly lack identified genetic cause, while 8% show associations with other cancer syndromes. We searched novel genetic associations for predisposition to UM, additional to already studied BAP1 and MBD4, by using targeted amplicon sequencing of 19 genes associated with UM, BAP1, or renal cell carcinoma in 270 consecutively enrolled Finnish patients with UM. Key UM drivers GNAQ, GNA11, CYSLTR2, PLCB4, EIF1AX, and SF3B1 lacked pathogenic germline variants. One patient carried the pathogenic BRCA1 variant c.3626del p.(Leu1209*), and one harbored a novel truncating MET variant c.252C > G p.(Tyr84*), classified as likely pathogenic. FLCN and BRCA2, previously identified with pathogenic variants in patients with UM, did not have such variants in our cohort. Two patients were heterozygous for a pathogenic recessive BLM variant c.2824-2A > T. None of the carriers of identified variants had familial UM. We identified BRCA1 and MET as genes with pathogenic germline variants in Finnish UM patients, each with a frequency of 0.4% (95% confidence interval, 0-2).
(© 2024 The Author(s). Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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