TERT promoter mutations in ocular melanoma distinguish between conjunctival and uveal tumours

Abstract

Background: Recently, activating mutations in the TERT promoter were identified in cutaneous melanoma. We tested a cohort of ocular melanoma samples for similar mutations.

Methods: The TERT promoter region was analysed by Sanger sequencing in 47 uveal (ciliary body or choroidal) melanomas and 38 conjunctival melanomas.

Results: Mutations of the TERT promoter were not identified in uveal melanomas, but were detected in 12 (32%) conjunctival melanomas. Mutations had a UV signature and were identical to those found in cutaneous melanoma.

Conclusion: Mutations of TERT promoter with UV signatures are frequent in conjunctival melanomas and favour a pathogenetic kinship with cutaneous melanomas. Absence of these mutations in uveal melanomas emphasises their genetic distinction from cutaneous and conjunctival melanomas.

Figure 1

Mutations identified in the TERT promoter. Representative electropherograms showing the wild-type sequence from a uveal melanoma sample (on top) and the mutations identified in three conjunctival melanoma samples –Chr.5:1295228C>T, Chr.5:1295242_43delinsTT, and Chr.5:1295250C>T (hg19 assembly). Mutations in the figure are labeled using the last three digits of the first nucleotide mutated (underlined). The black arrowheads indicate the respective nucleotide changes.