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

The Cancer Genome Atlas Research Network

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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. Seiler et al. report that 119 splicing factor genes carry putative driver mutations over 33 tumor types in TCGA. The most common mutations appear to be mutually exclusive and are associated with lineage-independent altered splicing. Samples with these mutations show deregulation of cell-autonomous pathways and immune infiltration.

Original languageEnglish (US)
Pages (from-to)282-296.e4
JournalCell Reports
Volume23
Issue number1
DOIs
StatePublished - Apr 3 2018

Fingerprint

Genes
Mutation
Neoplasms
Tumors
RNA
RNA Splicing
Atlases
Deregulation
Genome
Exome
RNA Sequence Analysis
RNA Splicing Factors
Infiltration
Hematologic Neoplasms
Oncogenes
Carcinogenesis

Keywords

  • cancer
  • FUBP1
  • mutation
  • RBM10
  • SF3B1
  • splicing
  • SRSF2
  • U2AF1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types. / The Cancer Genome Atlas Research Network.

In: Cell Reports, Vol. 23, No. 1, 03.04.2018, p. 282-296.e4.

Research output: Contribution to journalArticle

The Cancer Genome Atlas Research Network. / Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types. In: Cell Reports. 2018 ; Vol. 23, No. 1. pp. 282-296.e4.
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