Treatment of uveal melanoma (UM) patients with metastatic disease is unfortunately limited. Twenty percent of UM harbor a mutation in splicing factor gene SF3B1, suggesting that aberrant spliceosome functioning plays a vital role in tumorigenesis. Splicing inhibitors exploit the pref-erential sensitivity of spliceosome compromised leukemic cells to these compounds. We have studied the effect of splicing inhibitor E7107 using two UM cell lines and ex vivo cultured SF3B1 and BAP1 mutated primary UM tumor slices. These UM cell lines and ex vivo tumor slices were exposed for 24h to different concentrations of E7107. Tumor slices were stained with H&E and incubated with BAP1, MelanA, MIB-1 and caspase-3 antisera. E7107 exposed UM cell lines showed decreased cell viability and increased apoptosis with the largest effect sizes in SF3B1-mutated UM. A similar effect was observed upon exposure of E7107 on UM tumor slices. Addi-tionally, RNA was isolated for transcriptome analysis and the type and number of alternative and aberrant transcripts was evaluated. Ninety-seven transcripts had a decrease in aberrant transcripts in all samples after E7107 exposure, and this effect was mostly in intron retention. This study indicates / suggests that mutated SF3B1 UM cells are more sensitive to splicing inhib-itor E7107 compared to wild-type SF3B1 UM cells.
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