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Cancer Cell. 2015 Oct 12;28(4):515-528. doi: 10.1016/j.ccell.2015.08.013. Epub 2015 Oct 1.

The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers.

Author information

1
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
2
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
3
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Pathophysiology, College of Basic Medicine, China Medical University, Shenyang City, Liaoning Province 110001, China.
4
Department of Genetics, Stanford University, Stanford, CA 94305, USA.
5
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Division of Biostatistics, The University of Texas Health Science Center at Houston, School of Public Health, Houston TX 77030, USA.
6
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Women's Department, Haukeland University Hospital, Jonas Liesvei 72, 5053 Bergen, Norway.
7
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
8
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
9
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: gmills@mdanderson.org.
10
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: hliang1@mdanderson.org.

Abstract

Adenosine-to-inosine (A-to-I) RNA editing is a widespread post-transcriptional mechanism, but its genomic landscape and clinical relevance in cancer have not been investigated systematically. We characterized the global A-to-I RNA editing profiles of 6,236 patient samples of 17 cancer types from The Cancer Genome Atlas and revealed a striking diversity of altered RNA-editing patterns in tumors relative to normal tissues. We identified an appreciable number of clinically relevant editing events, many of which are in noncoding regions. We experimentally demonstrated the effects of several cross-tumor nonsynonymous RNA editing events on cell viability and provide the evidence that RNA editing could selectively affect drug sensitivity. These results highlight RNA editing as an exciting theme for investigating cancer mechanisms, biomarkers, and treatments.

PMID:
26439496
PMCID:
PMC4605878
DOI:
10.1016/j.ccell.2015.08.013
[Indexed for MEDLINE]
Free PMC Article

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