Molecular characteristics of conjunctival melanoma using whole-exome sequencing

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 CMusing next-generation whole-exome sequencing (WES). DESIGN, SETTING, AND PARTICIPANTS Whole-exome sequencingwas 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 analyseswere 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.