Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types.

Academic Article


  • Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in┬ácancer and may represent an underappreciated hallmark of tumorigenesis.
  • Published In

  • Cell Reports  Journal
  • Keywords

  • FUBP1, RBM10, SF3B1, SRSF2, U2AF1, cancer, mutation, splicing
  • Digital Object Identifier (doi)

    Author List

  • Seiler M; Peng S; Agrawal AA; Palacino J; Teng T; Zhu P; Smith PG; Cancer Genome Atlas Research Network; Buonamici S; Yu L
  • Start Page

  • 282
  • End Page

  • 296.e4
  • Volume

  • 23
  • Issue

  • 1