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Swarup Sai Swaminathan, David Sant, Gaofeng Wang, Anat Galor, Sander R Dubovy, Carol Karp; Whole Exome Sequencing of Conjunctival Melanoma. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3345.
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© ARVO (1962-2015); The Authors (2016-present)
We characterized genomic mutations present in a series of conjunctival melanomas in order to determine whether these malignancies are similar to uveal or skin melanomas. To our knowledge, this was the first whole exome sequencing (WXS) study of conjunctival melanomas, a technique that is unbiased in its evaluation of genomic mutations.
Patients with excised melanomas between 2006 and 2012 were identified. Formalin-fixed tissue was sent for WXS from a series of 6 patients. Mutation hotspots were identified using Sanger sequencing. Large proteins were excluded due to their high proclivity for random mutations.
In all 6 samples, mutations were noted in several genes associated with skin melanomas, such as BRAF, EGFR, APC, NF1, and FAT4. In addition, several genes not previously implicated in conjunctival melanomas were identified, including MYH1, MYH2, MXRA5, TENM2, and TRPM2. These proteins are implicated in extracellular matrix remodeling. All six samples had missense mutations noted to be present in over 30% of skin melanomas. None of the samples contained mutations in BAP1, a known oncogene strongly associated with Class 2 uveal melanomas. Two of the six patients had BRAF mutations, both who had recurrences and required further therapy.
Conjunctival melanomas appear to have a genetic profile more similar to skin melanomas rather than uveal melanomas. Several novel mutations have been identified using WXS. Further studies with larger sample sizes are required to confirm these findings, and to evaluate whether more aggressive tumors are correlated with specific mutations.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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