Jiang Chang 1 , Wenle Tan 2 , Zhiqiang Ling 3 , Ruibin Xi 4 , Mingming Shao 2 , Mengjie Chen 5 , 6 , Yingying Luo 2 , Yanjie Zhao 2 , Yun Liu 4 , Xiancong Huang 3 , Yuchao Xia 4 , Jinlin Hu 7 , Joel S. Parker 5 , 8 , David Marron 8 , Qionghua Cui 2 , Linna Peng 2 , Jiahui Chu 2 , Hongmin Li 2 , Zhongli Du 2 , Yaling Han 2 , Wen Tan 2 , Zhihua Liu 9 , Qimin Zhan 9 , Yun Li 5 , 10 , Weimin Mao a , 11 , Chen Wu b , 2 , Dongxin Lin 2
26 May 2017
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.
Oesophageal squamous-cell carcinoma (ESCC) is a leading cause of cancer death, and half of ESCC cases occur in China. Here, the authors provide an in depth genomic landscape for this disease and identify specific mutation signatures—one of which is linked to alcohol intake.