Bauer, Michael A.Ashby, CodyWardell, ChristopherBoyle, Eileen M.Ortiz, MariaFlynt, ErinThakurta, AnjanMorgan, GarethWalker, Brian A.2024-03-202024-03-202021-03-01Bauer MA, Ashby C, Wardell C, et al. Differential RNA splicing as a potentially important driver mechanism in multiple myeloma. Haematologica. 2021;106(3):736-745. Published 2021 Mar 1. doi:10.3324/haematol.2019.235424https://hdl.handle.net/1805/39355Disruption of the normal splicing patterns of RNA is a major factor in the pathogenesis of a number of diseases. Increasingly research has shown the strong influence that splicing patterns can have on cancer progression. Multiple Myeloma is a molecularly heterogeneous disease classified by the presence of key translocations, gene expression profiles and mutations but the splicing patterns in MM remains largely unexplored. We take a multifaceted approach to define the extent and impact of alternative splicing in MM. We look at the spliceosome component, SF3B1, with hotspot mutations (K700E and K666T/Q) shown to result in an increase in alternative splicing in other cancers. We discovered a number of differentially spliced genes in comparison of the SF3B1 mutant and wild type samples that included, MZB1, DYNLL1, TMEM14C and splicing related genes DHX9, CLASRP, and SNRPE. We identified a broader role for abnormal splicing showing clear differences in the extent of novel splice variants in the different translocation groups. We show that a high number of novel splice loci is associated with adverse survival and an ultra-high risk group. The enumeration of patterns of alternative splicing has the potential to refine MM classification and to aid in the risk stratification of patients.en-USAttribution-NonCommercial 4.0 InternationalAlternative splicingMultiple myelomaPhosphoproteinsRNA splicing factorsArticle