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

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 LuKenneth L. Scott, Jin Billy Li, Gordon B. Mills, Han Liang

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374 Scopus citations

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.

Original language	English (US)
Article number	2143
Pages (from-to)	515-528
Number of pages	14
Journal	Cancer cell
Volume	28
Issue number	4
DOIs	https://doi.org/10.1016/j.ccell.2015.08.013
State	Published - Oct 12 2015

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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Advanced Technology Genomics Core
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Functional Proteomics Reverse Phase Protein Array Core
Cytogenetics and Cell Authentication Core

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10.1016/j.ccell.2015.08.013

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Han, L., Diao, L., Yu, S., Xu, X., Li, J., Zhang, R., Yang, Y., Werner, H. M. J., Eterovic, A. K., Yuan, Y., Li, J., Nair, N., Minelli, R., Tsang, Y. H., Cheung, L. W. T., Jeong, K. J., Roszik, J., Ju, Z., Woodman, S. E., ... Liang, H. (2015). The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers. Cancer cell, 28(4), 515-528. Article 2143. https://doi.org/10.1016/j.ccell.2015.08.013

Han, L, Diao, L , Yu, S, Xu, X, Li, J, Zhang, R, Yang, Y, Werner, HMJ, Eterovic, AK, Yuan, Y, Li, J, Nair, N, Minelli, R, Tsang, YH, Cheung, LWT, Jeong, KJ, Roszik, J , Ju, Z , Woodman, SE , Lu, Y, Scott, KL, Li, JB, Mills, GB & Liang, H 2015, 'The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers', Cancer cell, vol. 28, no. 4, 2143, pp. 515-528. https://doi.org/10.1016/j.ccell.2015.08.013

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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.",

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

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AU - Zhang, Rui

AU - Yang, Yang

AU - Werner, Henrica M.J.

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AU - Nair, Nikitha

AU - Minelli, Rosalba

AU - Tsang, Yiu Huen

AU - Cheung, Lydia W.T.

AU - Jeong, Kang Jin

AU - Roszik, Jason

AU - Ju, Zhenlin

AU - Woodman, Scott E.

AU - Lu, Yiling

AU - Scott, Kenneth L.

AU - Li, Jin Billy

AU - Mills, Gordon B.

AU - Liang, Han

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AB - 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.

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

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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