• Anna E Koopmans, Kimberley Ober, Hendrikus J Dubbink, Dion Paridaens, Nicole C Naus, Stephan Belunek, Bart Krist, Edward Post, Ellen C Zwarthoff, Annelies de Klein, Robert M Verdijk, and Rotterdam Ocular Melanoma Study Group.
• Department of Ophthalmology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands Department of Clinical Genetics, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
• Invest. Ophthalmol. Vis. Sci. 2014 Sep 1; 55 (9): 6024-30.

PurposeHot-spot mutations in the promoter region of telomerase reverse transcriptase (TERT promoter mutations) occur frequently in cutaneous and conjunctival melanoma and are exceedingly rare in uveal melanoma. No information is available on the presence of these mutations in the conjunctival melanocytic precursor lesion primary acquired melanosis (PAM). We tested a cohort of uveal and conjunctival melanomas as well as conjunctival benign and premalignant melanocytic lesions for TERT promoter mutations in order to elucidate the role of these mutations in tumor progression.MethodsTERT promoter mutation analysis on fresh tumor DNA and DNA from formalin-fixed, paraffin-embedded specimens was performed by SNaPshot analysis in 102 uveal melanomas, 39 conjunctival melanomas, 26 PAM with atypia, 14 PAM without atypia, and 56 conjunctival nevi.ResultsMutations of the TERT promoter were not identified in conjunctival nevi or PAM without atypia, but were detected in 2/25 (8%) of PAM with atypia and 16/39 (41%) of conjunctival melanomas. A single TERT promoter mutation was detected in 102 uveal melanomas (1%).ConclusionsWe present the second documented case of TERT promoter mutation in uveal melanoma. In comparison with other types of melanoma, TERT promoter mutations occur at extremely low frequency in uveal melanoma. TERT promoter mutations are frequent in conjunctival melanoma and occur at lower frequency in PAM with atypia but were not detected in benign conjunctival melanocytic lesions. These findings favor a pathogenetic tumor progression role for TERT promoter mutations in conjunctival melanocytic lesions.Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

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