Related Experiment Video
Updated: Nov 23, 2025
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Genomic and transcriptomic landscape of conjunctival melanoma
Katarina Cisarova1,2, Marc Folcher3,4, Ikram El Zaoui1
1Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
Abstract:
Conjunctival melanoma (CJM) is a rare but potentially lethal and highly-recurrent cancer of the eye. Similar to cutaneous melanoma (CM), it originates from melanocytes. Unlike CM, however, CJM is relatively poorly characterized from a genomic point of view. To fill this knowledge gap and gain insight into the genomic nature of CJM, we performed whole-exome (WES) or whole-genome sequencing (WGS) of tumor-normal tissue pairs in 14 affected individuals, as well as RNA sequencing in a subset of 11 tumor tissues. Our results show that, similarly to CM, CJM is also characterized by a very high mutation load, composed of approximately 500 somatic mutations in exonic regions. This, as well as the presence of a UV light-induced mutational signature, are clear signs of the role of sunlight in CJM tumorigenesis. In addition, the genomic classification of CM proposed by TCGA seems to be well-applicable to CJM, with the presence of four typical subclasses defined on the basis of the most frequently mutated genes: BRAF, NF1, RAS, and triple wild-type. In line with these results, transcriptomic analyses revealed similarities with CM as well, namely the presence of a transcriptomic subtype enriched for immune genes and a subtype enriched for genes associated with keratins and epithelial functions. Finally, in seven tumors we detected somatic mutations in ACSS3, a possible new candidate oncogene. Transfected conjunctival melanoma cells overexpressing mutant ACSS3 showed higher proliferative activity, supporting the direct involvement of this gene in the tumorigenesis of CJM. Altogether, our results provide the first unbiased and complete genomic and transcriptomic classification of CJM.
Insights
Conjunctival melanoma (CJM), a rare eye cancer, shares genomic similarities with skin melanoma, including high mutation rates and UV light damage signatures. This study provides the first comprehensive genomic and transcriptomic classification of CJM.
Area of Science:
- Ophthalmology
- Oncology
- Genomics
Background:
- Conjunctival melanoma (CJM) is a rare, aggressive eye cancer originating from melanocytes, with limited genomic characterization compared to cutaneous melanoma (CM).
- Understanding CJM's genomic landscape is crucial for developing targeted therapies and improving patient outcomes.
Purpose of the Study:
- To comprehensively characterize the genomic and transcriptomic features of conjunctival melanoma.
- To establish a genomic classification for CJM and identify potential new driver genes.
Main Methods:
- Whole-exome (WES) and whole-genome sequencing (WGS) were performed on 14 tumor-normal pairs.
- RNA sequencing was conducted on 11 tumor tissues.
- Analysis included mutation load, mutational signatures, gene expression, and identification of candidate oncogenes.
Main Results:
- CJM exhibits a high mutation load (~500 exonic mutations) and a UV-induced mutational signature, implicating sunlight in its development.
- Genomic classification based on TCGA's CM subclasses (BRAF, NF1, RAS, triple wild-type) is applicable to CJM.
- Transcriptomic analysis revealed subtypes enriched for immune or epithelial-associated genes.
- Somatic mutations in ACSS3 were detected in seven tumors, with overexpression enhancing cell proliferation, suggesting ACSS3 as a potential oncogene.
Conclusions:
- This study provides the first unbiased genomic and transcriptomic classification of conjunctival melanoma.
- CJM shares significant molecular similarities with cutaneous melanoma.
- ACSS3 is identified as a potential novel oncogene in conjunctival melanoma tumorigenesis.
More Related Videos
06:46Ortho- and Ectopic Zebrafish Xeno-Engraftment of Ocular Melanoma to Recapitulate Primary Tumor and Experimental Metastasis Development
Published on: September 4, 2021
05:46Implantation and Evaluation of Melanoma in the Murine Choroid via Optical Coherence Tomography
Published on: December 2, 2022
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:17The Tumor Microenvironment
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:21Cancers Originate from Somatic Mutations in a Single Cell
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...