Elevated RNA Editing Activity Is a Major Contributor to Transcriptomic Diversity in Tumors

Nurit Paz-Yaacov, Lily Bazak, Ilana Buchumenski, Hagit T. Porath, Miri Danan-Gotthold, Binyamin A. Knisbacher, Eli Eisenberg, Erez Y. Levanon

Research output: Contribution to journalArticlepeer-review

213 Scopus citations

Abstract

Genomic mutations in key genes are known to drive tumorigenesis and have been the focus of much attention in recent years. However, genetic content also may change farther downstream. RNA editing alters the mRNA sequence from its genomic blueprint in a dynamic and flexible way. A few isolated cases of editing alterations in cancer have been reported previously. Here, we provide a transcriptome-wide characterization of RNA editing across hundreds of cancer samples from multiple cancer tissues, and we show that A-to-I editing and the enzymes mediating this modification are significantly altered, usually elevated, in most cancer types. Increased editing activity is found to be associated with patient survival. As is the case with somatic mutations in DNA, most of these newly introduced RNA mutations are likely passengers, but a few may serve as drivers that may be novel candidates for therapeutic and diagnostic purposes.

Original languageEnglish
Pages (from-to)267-276
Number of pages10
JournalCell Reports
Volume13
Issue number2
DOIs
StatePublished - 13 Oct 2015

Bibliographical note

Funding Information:
We thank Gilad Finkelshtein and Michal Barak for downloading the data, Gidi Rechavi for fruitful discussion, Moran Gal and Jasmine Jacob-Hirsch for assisting with functional analysis, and Orshay Gabay for graphical help. The results shown here are based on data generated by the TCGA Research Network ( http://cancergenome.nih.gov/ ). This work was supported by the European Research Council (grant 311257), the Leon and Maria Taubenblatt Prize for Excellence in Medical Research, the I-CORE Program of the Planning and Budgeting Committee in Israel (grants 41/11 and 1796/12), and the Israel Science Foundation (1380/14 [E.Y.L.] and 379/12 [E.E.]).

Publisher Copyright:
© 2015 The Authors.

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