Bilateral Uveal Melanoma: An Insight into Genetic Predisposition in Four New Unrelated Patients and Review of Published Cases

• Published in: Journal of clinical medicine 2024-05, Vol.13 (11), p.3035
• Main Authors: Silva-Rodríguez, Paula, Bande, Manuel, Pardo, María, Domínguez, Fernando, Loidi, Lourdes, Blanco-Teijeiro, María José
• Format: Article
• Language: English
• Subjects: Breast cancer; Development and progression; Genes; Genetic testing; Genomes; Genomics; Melanoma; Metastasis; Mutation; Patients; Radiation therapy; Ultrasonic imaging; Visual acuity; White people
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm13113035

: Primary bilateral uveal melanoma (BUM) is an exceptionally rare form of uveal melanoma (UM). This study aimed to explore the potential existence of a genetic predisposition towards the development of BUM. : We employed an exome sequencing approach on germline DNA from four unrelated patients diagnosed with BUM, seeking pathogenic or likely pathogenic variants indicative of a genetic predisposition to UM. : None of the patients exhibited pathogenic variants in the gene. However, loss-of-function (LoF) variants in the and genes were identified in two of the BUM patients. For patients BUM1 and BUM2, no pathogenic/likely pathogenic variants of significant clinical relevance to BUM were found to warrant inclusion in this report. : Our findings suggest the presence of yet-to-be-discovered genes that may contribute to UM predisposition, as evidenced by the absence of pathogenic variants in known UM predisposition genes among the four BUM patients studied. The and genes emerge as noteworthy candidates for further investigation regarding their role in genetic predisposition to UM. Specifically, the potential role of UM as a candidate cancer within the spectrum of cancers linked to pathogenic variants in the gene and other genes associated with the complex warrants further examination. Additional functional studies are necessary to support or challenge this hypothesis.