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

Journal Article (Journal 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 cancer and may represent an underappreciated hallmark of tumorigenesis.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • April 3, 2018

Published In

Volume / Issue

  • 23 / 1

Start / End Page

  • 282 - 296.e4

PubMed ID

  • 29617667

Pubmed Central ID

  • PMC5933844

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2018.01.088


  • eng

Conference Location

  • United States