DNA REPAIR AND CELL CYCLE ARE SYNTHETIC LETHAL PATHWAYS IN SRSF2P95H MUTATED CELLS

Abstract

Current strategies to target cells with mutations in the RNA splicing machinery have focused on the disruption of normal splicing activities. However, splicing inhibitors are also toxic to wild-type cells as has been demonstrated in the clinical trial of spliceosome inhibitors. To understand splicing changes when there is a mutation in the RNA splicing factors, we analyzed splicing across a collated collection of SRSF2P95H mutant samples from both human and murine, incorporating multiple myeloid cancer types (AML, MDS, CMML). Using the gene lists of transcripts that were mis-spliced across multiple datasets we found that DNA repair and cell cycle are represented amongst the top mis-spliced p..