Characterization of RNA editome in primary and metastatic lung adenocarcinomas
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Lihua Peng1,2,*, Leo J Lee2,3,*, Heng Xiong2, Hong Su2, Junhua Rao2, Dakai Xiao4,5,6, Jianxing He4,5,7, Kui Wu2,8, Dongbing Liu2
1BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China
2BGI-Shenzhen, Shenzhen 518083, China
3Department of Electrical and Computer Engineering, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3G4, Canada
4Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
5Guangzhou Institute of Respiratory Disease & State Key Laboratory of Respiratory Disease, Guangzhou 510120, China
6Research Center for Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
7National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China
8Department of Biology, University of Copenhagen, Copenhagen N DK-2200, Denmark
*These authors have contributed equally to this work
Dongbing Liu, email: firstname.lastname@example.org
Keywords: lung adenocarcinoma, RNA editing, hyper-editing, primary, metastatic
Received: May 27, 2016 Accepted: November 21, 2016 Published: December 21, 2016
RNA editing results in post-transcriptional modification and could potentially contribute to carcinogenesis. However, RNA editing in advanced lung adenocarcinomas has not yet been studied. Based on whole genome and transcriptome sequencing data, we identified 1,071,296 RNA editing events from matched normal, primary and metastatic samples contributed by 24 lung adenocarcinoma patients, with 91.3% A-to-G editing on average, and found significantly more RNA editing sites in tumors than in normal samples. To investigate cancer relevant editing events, we detected 67,851 hyper-editing sites in primary and 50,480 hyper-editing sites in metastatic samples. 46 genes with hyper-editing in coding regions were found to result in amino acid alterations, while hundreds of hyper-editing events in non-coding regions could modulate splicing or gene expression, including genes related to tumor stage or clinic prognosis. Comparing RNA editome of primary and metastatic samples, we also discovered hyper-edited genes that may promote metastasis development. These findings showed a landscape of RNA editing in matched normal, primary and metastatic tissues of lung adenocarcinomas for the first time and provided new insights to understand the molecular characterization of this disease.
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