Large-scale cancer sequencing efforts identified highly recurrent mutations in core spliceosome component SF3B1 at restricted sites (i.e., 50% at K700E), implicating role of altered RNA splicing in CLL.
Mutated SF3B1: higher incidence in refractory/relapsed CLL.
Study downstream pathways modified by mutated SF3B1 and its effetcs in disease.
Hypothesis: altered splicing associated with this driver.
Methods: 22 CLL cases, 9 mutant and 13 wild-type SF3B1; generated RNA-seq data, identified splicing effects associated with SF3B1 mutation using JuncBASE (Junction Based Analysis of Spliced Events).
SF3B1 catalyzes U2 snRNP, critical for initial formation of core spliceosome at 3’ exon/intron boundaries.
Analysis identified pervasive changes in 3’ splice site of 642 introns associated with SF3B1 mutation (p < 0.05).
This alterations in 3’ splice site - caused both partial exon skipping and partial intron retention, equivalently.
- Identified candidate list of several genes, which carry high rate of SF3B1 mutation, with roles in B cell biology.
- These analyses will guide selection: candidates genes for downstream functional assessment; identify variants with highest oncogenicity.
View the original abstract on the ASH website.
