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

• Published in: Cell reports (Cambridge) 2015-10, Vol.13 (2), p.267-276
• Main Authors: Paz-Yaacov, Nurit, Bazak, Lily, Buchumenski, Ilana, Porath, Hagit T., Danan-Gotthold, Miri, Knisbacher, Binyamin A., Eisenberg, Eli, Levanon, Erez Y.
• Format: Article
• Language: English
• Subjects: Breast Neoplasms - genetics; Carcinoma - genetics; Female; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms - genetics; Male; Mutation; Prostatic Neoplasms - genetics; RNA Editing; Transcriptome; Up-Regulation
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2015.08.080

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. [Display omitted] •Level of A-to-I RNA editing by ADAR enzymes is elevated in various cancer types•Extensive editing in cancer introduces RNA diversity or RNA mutations•RNA modification events in tumors are as abundant as genomic DNA mutations•Increased editing activity is associated with poor prognosis Paz-Yaacov et al. show that several types of cancer are accompanied by elevated activity of RNA editing, a process that changes the sequence of RNA from that encoded in the genome. Similar to genomic mutations, this mechanism results in multiple changes of the genetic information, which may be beneficial for cancer progression.