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Brief Report
December 2017

Molecular Characteristics of Conjunctival Melanoma Using Whole-Exome Sequencing

Author Affiliations
  • 1Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
  • 2Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida
  • 3John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida
  • 4Department of Ophthalmology, Miami Veteran Affairs Medical Center, Miami, Florida
  • 5Florida Lions Ocular Pathology Laboratory, University of Miami Miller School of Medicine, Miami, Florida
JAMA Ophthalmol. 2017;135(12):1434-1437. doi:10.1001/jamaophthalmol.2017.4837
Key Points

Question  What mutations can be identified with whole-exome sequencing (WES) of conjunctival melanoma (CM)?

Findings  With WES, CM was found to harbor mutations in BRAF, NRAS, and NF1; previously unreported mutations in EGFR, APC, TERT and other cancer-associated genes; and the C→T mutation signature consistent with UV-induced DNA damage. The most common chromosomal alteration was 6p gain.

Meaning  Whole-exome sequencing might enable the detection of molecular mutations targetable by cancer therapies and provide insight into the pathogenesis of CM.


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.

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