Abstract 3420: TERT promoter mutations are rare in uveal melanoma

Abstract

Abstract Uveal melanoma is the most frequent primary tumor of the eye. It is molecularly clearly distinct from cutaneous melanoma and shows a different pattern of driver mutations. The influence of sunlight UV-exposure on the etiology of uveal melanoma is matter of debate. The recent identification of driver mutations in the promoter of the telomerase reverse transcriptase (TERT) gene with UV induced cytidine-to-thymidine transitions in cutaneous melanoma prompted us to investigate whether these mutations also occur in uveal melanoma. We also analyzed the frequency of other recently discovered uveal melanoma specific mutations in the genes GNAQ, GNA11, BAP1, SF3B1, and EIFAX1, and we analyzed the association of these mutation with histopathological and clinical features including progression free survival. Finally, we analyzed TERT expression in these tumors. The mutation frequencies observed confirmed the prevalence of GNAQ mutations in cases with disomy of chromosome 3 that have a better prognosis whereas GNA11 was more frequent in monosomic cases. Together these two mutations account for more than 85% of the cases. BAP1 mutations are associated with chromosome 3 monosomy but not with progression free survival. SF3B1 and EIF1AX mutations occur in 10.3 and 22.5% of uveal melanomas, in disomic cases only. We detected a TERT mutation in only one case of a 57-year old white male with clinical and histo-pathological features typical for uveal melanoma. The tumor showed mutations in GNA11 and EIF1AX. No mutations were detected in GNAQ, BAP1, and SF3B1. Both copies of chromosome 3 were retained. Several tumors among which the one carrying the TERT promoter mutation showed elevated TERT expression. These data indicate that TERT mutations are rare in uveal melanoma, consistent with a reduced etiological influence of sunlight. No conclusion can be drawn on the potential influence of TERT mutations on tumor progression. Citation Format: Adriana Agnese AMARO, Marina Gualco, Maria Dono, Ulrich Pfeffer, Irena Maric, Carlo Mosci. TERT promoter mutations are rare in uveal melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3420. doi:10.1158/1538-7445.AM2014-3420