Splice of Life for Cancer: Missplicing of PPP2R5A by Mutant SF3B1 Leads to MYC Stabilization and Tumorigenesis

Although mutations in SF3B1 are the most common RNA-splicing factor mutations in cancer, determining the downstream missplicing events that drive tumorigenesis has remained challenging. Liu and colleagues present a model by which mutant SF3B1 tumors displayed high levels of oncogenic MYC activity through the missplicing of PP2A-B56α, a key post-translational regulator of MYC stability, providing a new therapeutic target and driver of SF3B1-mediated tumorigenesis. See related article by Liu et al., p. 806 .