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Review
. 2023 Aug 23;14(9):1668.
doi: 10.3390/genes14091668.

Genetic Aspects of Conjunctival Melanoma: A Review

Emily Chang  1 , Hakan Demirci  1 , F Yesim Demirci  2
Affiliations
Review

Genetic Aspects of Conjunctival Melanoma: A Review

Emily Chang et al. Genes (Basel). .

Abstract

Conjunctival melanoma (CM) is a rare but aggressive cancer. Over the past decade, molecular studies using rapidly advancing technologies have increasingly improved our understanding of CM genetics. CMs are mainly characterized by dysregulated MAPK and PI3K/AKT/mTOR pathways, driven by commonly mutated (BRAF, NRAS, NF1) or less commonly mutated (KIT, PTEN) genes. Another group of genes frequently mutated in CMs include TERT and ATRX, with known roles in telomere maintenance and chromatin remodeling/epigenetic regulation. Uveal melanoma-related genes (BAP1, SF3B1, GNAQ/11) can also be mutated in CMs, albeit infrequently. Additional CM-related mutated genes have increasingly been identified using more comprehensive genetic analyses, awaiting further confirmation in additional/larger studies. As a tumor arising in a partly sun-exposed mucosal tissue, CM exhibits a distinct genomic profile, including the frequent presence of an ultraviolet (UV) signature (and high mutational load) and also the common occurrence of large structural variations (distributed across the genome) in addition to specific gene mutations. The knowledge gained from CM genetic studies to date has led to new therapeutic avenues, including the use of targeted and/or immuno-therapies with promising outcomes in several cases. Accordingly, the implementation of tumor genetic testing into the routine clinical care of CM patients holds promise to further improve and personalize their treatments. Likewise, a growing knowledge of poor prognosis-associated genetic changes in CMs (NRAS, TERT, and uveal melanoma signature mutations and chromosome 10q deletions) may ultimately guide future strategies for prognostic testing to further improve clinical outcomes (by tailoring surveillance and considering prophylactic treatments in patients with high-risk primary tumors).

Keywords: UV signature; conjunctival melanoma; copy number alterations; genes; genetic; molecular; mutations; pathways; structural variations; tumor mutational burden.

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Conflict of interest statement

H.D. serves on the advisory boards of Castle Bioscience and Aura Bioscience outside the submitted work. No other disclosures to be reported.

Figures

Figure 1
Figure 1
Regions of the conjunctiva affected by melanoma. Conjunctiva (blue line on the left panel) is a partly sun-exposed tissue, and bulbar conjunctiva is more commonly affected by melanoma than non-bulbar (caruncular, forniceal, and palpebral) conjunctiva (this figure was created with BioRender.com and Microsoft PowerPoint).
Figure 2
Figure 2
Genetic alterations and affected pathways/genes in primary conjunctival melanomas. Frequently mutated driver genes are marked in bold (this figure was created with BioRender.com and Microsoft PowerPoint).
See this image and copyright information in PMC

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