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Differential RNA splicing as a potentially important driver mechanism in multiple myeloma
- Source :
- Haematologica
- Publication Year :
- 2020
- Publisher :
- Ferrata Storti Foundation (Haematologica), 2020.
-
Abstract
- 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.
- Subjects :
- Spliceosome
RNA Splicing
Computational biology
Biology
Article
03 medical and health sciences
0302 clinical medicine
Gene expression
Humans
splice
Gene
030304 developmental biology
0303 health sciences
Serine-Arginine Splicing Factors
Alternative splicing
Wild type
RNA
Hematology
Phosphoproteins
Alternative Splicing
030220 oncology & carcinogenesis
Mutation
RNA splicing
Spliceosomes
RNA Splicing Factors
Multiple Myeloma
Subjects
Details
- ISSN :
- 15928721 and 03906078
- Volume :
- 106
- Database :
- OpenAIRE
- Journal :
- Haematologica
- Accession number :
- edsair.doi.dedup.....23c56d8587a2b70d3f12ca665a337b58