Synthetic Lethal and Convergent Biological Effects of Cancer-Associated Spliceosomal Gene Mutations. Academic Article uri icon

Overview

abstract

  • Mutations affecting RNA splicing factors are the most common genetic alterations in myelodysplastic syndrome (MDS) patients and occur in a mutually exclusive manner. The basis for the mutual exclusivity of these mutations and how they contribute to MDS is not well understood. Here we report that although different spliceosome gene mutations impart distinct effects on splicing, they are negatively selected for when co-expressed due to aberrant splicing and downregulation of regulators of hematopoietic stem cell survival and quiescence. In addition to this synthetic lethal interaction, mutations in the splicing factors SF3B1 and SRSF2 share convergent effects on aberrant splicing of mRNAs that promote nuclear factor κB signaling. These data identify shared consequences of splicing-factor mutations and the basis for their mutual exclusivity.

publication date

  • August 13, 2018

Research

keywords

  • Mutation
  • Neoplasms
  • Spliceosomes

Identity

PubMed Central ID

  • PMC6373472

Scopus Document Identifier

  • 85050672714

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2018.07.003

PubMed ID

  • 30107174

Additional Document Info

volume

  • 34

issue

  • 2