Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations

Jiang Chang(Huazhong University of Science and Technology), Wenle Tan(Chinese Academy of Medical Sciences & Peking Union Medical College), Zhi‐Qiang Ling(Zhejiang Cancer Hospital), Ruibin Xi(Peking University), Mingming Shao(Chinese Academy of Medical Sciences & Peking Union Medical College), Mengjie Chen(University of North Carolina at Chapel Hill), Yingying Luo(Chinese Academy of Medical Sciences & Peking Union Medical College), Yanjie Zhao(Chinese Academy of Medical Sciences & Peking Union Medical College), Yun Liu(Peking University), Xiancong Huang(Zhejiang Cancer Hospital), Yuchao Xia(Peking University), Jinlin Hu(Zhejiang Cancer Hospital), Joel S. Parker(University of North Carolina at Chapel Hill), David Marron(University of North Carolina at Chapel Hill), Qionghua Cui(Chinese Academy of Medical Sciences & Peking Union Medical College), Linna Peng(Chinese Academy of Medical Sciences & Peking Union Medical College), Jiahui Chu(Chinese Academy of Medical Sciences & Peking Union Medical College), Hongmin Li(Chinese Academy of Medical Sciences & Peking Union Medical College), Zhongli Du(Chinese Academy of Medical Sciences & Peking Union Medical College), Yaling Han(Chinese Academy of Medical Sciences & Peking Union Medical College), Wen Tan(Chinese Academy of Medical Sciences & Peking Union Medical College), Zhihua Liu(Chinese Academy of Medical Sciences & Peking Union Medical College), Qimin Zhan(Chinese Academy of Medical Sciences & Peking Union Medical College), Yun Li(University of North Carolina at Chapel Hill), Weimin Mao(Zhejiang Cancer Hospital), Chen Wu(Chinese Academy of Medical Sciences & Peking Union Medical College), Dongxin Lin(Chinese Academy of Medical Sciences & Peking Union Medical College)
Nature Communications
May 26, 2017
10.1038/ncomms15290
Cited by 259Open Access
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Abstract

Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1-E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28. The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer.

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