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

Leng Han; Lixia Diao; Shuangxing Yu; Xiaoyan Xu; Jie Li; Rui Zhang; Yang Yang; Henrica M J Werner; A Karina Eterovic; Yuan Yuan; Jun Li; Nikitha Nair; Rosalba Minelli; Yiu Huen Tsang; Lydia W T Cheung; Kang Jin Jeong; Jason Roszik; Zhenlin Ju; Scott E Woodman; Yiling Lu; Kenneth L Scott; Jin Billy Li; Gordon B Mills; Han Liang

doi:10.1016/j.ccell.2015.08.013

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

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

Authors

Leng Han¹, Lixia Diao¹, Shuangxing Yu², Xiaoyan Xu³, Jie Li², Rui Zhang⁴, Yang Yang⁵, Henrica M J Werner⁶, A Karina Eterovic², Yuan Yuan¹, Jun Li¹, Nikitha Nair⁷, Rosalba Minelli⁷, Yiu Huen Tsang⁷, Lydia W T Cheung², Kang Jin Jeong², Jason Roszik⁸, Zhenlin Ju¹, Scott E Woodman⁸, Yiling Lu², Kenneth L Scott⁷, Jin Billy Li⁴, Gordon B Mills⁹, Han Liang¹⁰

Affiliations

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenosine / metabolism*
Antineoplastic Agents / pharmacology
Cell Line, Tumor
Cell Survival
Genome, Human
Humans
Inosine / metabolism*
Neoplasms / genetics*
Neoplasms / pathology
RNA Editing*

Substances

Antineoplastic Agents
Inosine
Adenosine

Abstract

Publication types

MeSH terms

Substances

Grants and funding