Genetic and Epigenetic Features of Uveal Melanoma—An Overview and Clinical Implications

Abstract

Uveal melanoma (UM) is rare, but it is the most common primary intraocular malignancy among adults. This review represents the molecular, genetic, and immunobiological mechanisms involved in UM carcinogenesis and progression, as well as data about the association of chromosomal changes, genetic mutations, selective proteins, and biochemical biomarkers with the clinical implications of UM. Genetic analysis has the potential to identify patients with a high risk of UM metastasis, enabling management that is more effective and allowing for the follow-up of patients. Advancements in molecular characterization of UM offer opportunities to develop targeted therapeutic strategies by focusing on relevant signaling pathways. Changes in miRNA expression could be useful in the diagnosis and prognosis of UM, due to unique miRNA profiles in melanoma cells or tissue and its association with metastasis. Although liver function tests do not provide enough data on the prognosis of UM, due to the high frequency of liver metastasis, liver function tests (LFTs) might be useful indicators; however, the absence of rising LFT values cannot lead to the exclusion of liver metastases. Molecular analysis of tumor tissue will allow us to identify patients with the added benefit of new therapeutic agents and provide a better insight into melanoma pathogenesis and its biological behavior.

From Molecular Biology to Novel Immunotherapies and Nanomedicine in Uveal Melanoma

“…Mutations in the BAP1 gene most often result in the early termination of the BAP1 protein and may affect its ubiquitin carboxyl-terminal hydrolase domain, thereby modifying its deubiquitinase activity. Because BAP1 has interactions with multiple proteins and signaling pathways, including the tumor suppressor BRCA1 gene, it plays a vital role in preserving genome stability and DNA damage response [11][12][13]. Around 10-20% of uveal melanoma cases display mutations in the splicing factor 3B subunit 1 (SF3B1) gene.…”

“…The X-linked eukaryotic translation initiation factor 1A protein is a key player in overseeing the initiation of protein translation. Mutations in EIF1AX can cause the mis-selection of start sites, resulting in the inhibited translation of canonical transcripts or potentially elevating the expression of oncogenes [8,[13][14][15][16][17]. Again, BAP1, SF3B1, and EIF1AX mutations are mutually exclusive.…”

“…Mutations in genes including GNAQ, GNA11, SF3B1, EIF1AX, BAP-1, and PRAME are important in assessing prognoses. Epigenetic mechanisms regulated by non-coding RNAs (ncRNA) including microRNAs and long non-coding RNAs are also deregulated in UM, including miR-513a-5p, miR-182, miR-211, miR-137, miR-20a, and miR-27a [7,8,13,18].…”

Biological characteristics and clinical management of uveal and conjunctival melanoma

“…In contrast to CM, there is a greater amount of data associated with studies on miRNA expression in UM. Our earlier literature review included comprehensive findings from many studies that examined the function and variations in miRNA expression in UM [ 10 ].…”

Special Issue “The Molecular and Cellular Pathophysiologic Mechanisms Underlying Ocular Diseases and Emerging Therapies”

“…Finally, in a comprehensive review article by Pašalić et al [20], current knowledge regarding the genetic and epigenetic characteristics of uveal melanoma (UM) is summarized. Molecular research has enhanced our understanding of the genetic and epigenetic mechanisms that underlie the biological behavior of UM.…”