Identification of recurrent regulated alternative splicing events across human solid tumors

Nucleic Acids Res. 2015 May 26;43(10):5130-44. doi: 10.1093/nar/gkv210. Epub 2015 Apr 23.

Abstract

Cancer is a complex disease that involves aberrant gene expression regulation. Discriminating the modified expression patterns driving tumor biology from the many that have no or little contribution is important for understanding cancer molecular basis. Recurrent deregulation patterns observed in multiple cancer types are enriched for such driver events. Here, we studied splicing alterations in hundreds of matched tumor and normal RNA-seq samples of eight solid cancer types. We found hundreds of cassette exons for which splicing was altered in multiple cancer types and identified a set of highly frequent altered splicing events. Specific splicing regulators, including RBFOX2, MBNL1/2 and QKI, appear to account for many splicing alteration events in multiple cancer types. Together, our results provide a first global analysis of regulated splicing alterations in cancer and identify common events with a potential causative role in solid tumor development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Exons
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • RNA Splicing Factors
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Regulatory Sequences, Ribonucleic Acid
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism

Substances

  • QKI protein, human
  • RBFOX2 protein, human
  • RNA Splicing Factors
  • RNA-Binding Proteins
  • Regulatory Sequences, Ribonucleic Acid
  • Repressor Proteins