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Updated: Feb 19, 2026
Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
Published on: October 18, 2013
Molecular Characteristics of Conjunctival Melanoma Using Whole-Exome Sequencing
Swarup S Swaminathan1, Matthew G Field1,2, David Sant3
1Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
Importance:
Conjunctival melanoma (CM) is a highly aggressive ocular cancer for which treatment options are limited; the molecular pathogenesis is poorly understood.
Objective:
To identify the molecular characteristics of CM using next-generation whole-exome sequencing (WES).
Design, Setting, And Participants:
Whole-exome sequencing was performed on tumor DNA extracted from the archived specimens of 5 patients with CM who had been treated with surgical excision between 2006 and 2011. These samples were analyzed at a tertiary academic ocular oncology referral center using a customized bioinformatic pipeline.
Main Outcomes And Measures:
Sample analyses were designed to detect driver mutations, chromosome copy number aberrations, and mutation signatures.
Results:
The study’s 5 patients ranged in age from 51 to 77 years. Four of the 5 were female, and all were white. Mutations were detected in known oncogenes, including BRAF, NRAS, NF1, EGFR, ALK, TERT, and APC. None of the mutations associated with uveal melanoma were found. All samples demonstrated a C→T mutation signature typical of UV-induced DNA damage. The most common CNA was a gain in chromosome 6p.
Conclusions And Relevance:
In these 5 patients, WES allowed identification of mutations that can be targeted with therapy and supported the role of UV light in CM pathogenesis. These findings indicate a need for larger studies to evaluate the diagnostic, prognostic, and therapeutic value of WES for CM.
Insights
Whole-exome sequencing identified targetable mutations in conjunctival melanoma (CM), a rare ocular cancer. Findings suggest a role for UV light in CM development, warranting further investigation.
Area of Science:
- Ophthalmology
- Oncology
- Genetics
Background:
- Conjunctival melanoma (CM) is an aggressive ocular cancer with limited treatment options.
- The molecular underpinnings of CM remain poorly understood.
Purpose of the Study:
- To elucidate the molecular characteristics of conjunctival melanoma using next-generation whole-exome sequencing (WES).
Main Methods:
- Whole-exome sequencing (WES) was performed on tumor DNA from 5 CM patients.
- A customized bioinformatics pipeline was used to analyze samples for driver mutations, copy number aberrations, and mutation signatures.
Main Results:
- Mutations were identified in oncogenes including BRAF, NRAS, NF1, EGFR, ALK, TERT, and APC.
- A C→T mutation signature indicative of UV-induced DNA damage was present in all samples.
- The most frequent copy number aberration was a gain in chromosome 6p.
Conclusions:
- WES identified targetable mutations and supported the role of UV light in CM pathogenesis.
- Larger studies are needed to assess the diagnostic, prognostic, and therapeutic potential of WES for CM.
