The landscape of somatic mutation in sporadic Chinese colorectal cancer

// Zhe Liu 1, 3, * , Chao Yang 2, * , Xiangchun Li 2 , Wen Luo 2 , Bhaskar Roy 2 , Teng Xiong 2 , Xiuqing Zhang 2 , Huanming Yang 2, 4 , Jian Wang 2, 4 , Zhenhao Ye 5 , Yang Chen 5 , Jinghe Song 6 , Shuai Ma 6 , Yong Zhou 2 , Min Yang 1, 7 , Xiaodong Fang 2 and Jie Du 1 1 Beijing Anzhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Collaborative Innovation Center for Cardiovascular Disorders, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing, China 2 BGI Genomics, BGI-Shenzhen, Shenzhen, China 3 Beijing Advanced Innovation Center for Big Data and Brain Computing (BDBC), Beihang University, Beijing, China 4 James D. Watson Institute of Genome Sciences, Hangzhou, China 5 The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China 6 SKLSDE Lab, Beihang University, Beijing, China 7 State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China * These authors equally contribution to this work Correspondence to: Yong Zhou, email: zhouyong@bgi.com Min Yang, email: ymcq124@163.com Xiaodong Fang, email: fangxd@genomics.cn Jie Du, email: jdu@bcm.edu Keywords: colorectal cancer; whole-exome sequencing; disease etiology; Chinese patients; mutation spectrum Abbreviations: CRC: colorectal cancer; TCGA: the cancer genome atlas; SNV: single nucleotide variation; InDel: insertion and deletion Received: August 02, 2017      Accepted: March 06, 2018      Published: June 08, 2018 ABSTRACT Colorectal cancer is the fifth prevalent cancer in China. Nevertheless, a large-scale characterization of Chinese colorectal cancer mutation spectrum has not been carried out. In this study, we have performed whole exome-sequencing analysis of 98 patients’ tumor samples with matched pairs of normal colon tissues using Illumina and Complete Genomics high-throughput sequencing platforms. Canonical CRC somatic gene mutations with high prevalence (>10%) have been verified, including TP53 , APC , KRAS , SMAD4 , FBXW7 and PIK3CA . PEG3 is identified as a novel frequently mutated gene (10.6%). APC and Wnt signaling exhibit significantly lower mutation frequencies than those in TCGA data. Analysis with clinical characteristics indicates that APC gene and Wnt signaling display lower mutation rate in lymph node positive cancer than negative ones, which are not observed in TCGA data. APC gene and Wnt signaling are considered as the key molecule and pathway for colorectal cancer initiation, and these findings greatly undermine their importance in tumor progression for Chinese patients. Taken together, the application of next-generation sequencing has led to the determination of novel somatic mutations and alternative disease mechanisms in colorectal cancer progression, which may be useful for understanding disease mechanism and personalizing treatment for Chinese patients.