Differential RNA splicing as a potentially important driver mechanism in multiple myeloma

Journal article

Disruption 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

Authors: Bauer, MA; Ashby, C; Wardell, C; Boyle, EM; Ortiz, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Ferrata Storti Foundation
• Journal: Haematologica
• Volume: 106
• Issue: 3
• Pages: 736-745
• Publication date: 2020-02-20
• DOI: 10.3324/haematol.2019.235424
• EISSN: 1592-8721
• ISSN: 0390-6078
• Language: English
• Keywords: Computational biology; Intron; Messenger RNA; Gene; Alternative splicing; Genetics; RNA splicing; RNA; Spliceosome; Biology; Splicing factor