The landscape of somatic mutation in sporadic Chinese colorectal cancer
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Zhe Liu1,3,*, Chao Yang2,*, Xiangchun Li2, Wen Luo2, Bhaskar Roy2, Teng Xiong2, Xiuqing Zhang2, Huanming Yang2,4, Jian Wang2,4, Zhenhao Ye5, Yang Chen5, Jinghe Song6, Shuai Ma6, Yong Zhou2, Min Yang1,7, Xiaodong Fang2 and Jie Du1
1Beijing 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
2BGI Genomics, BGI-Shenzhen, Shenzhen, China
3Beijing Advanced Innovation Center for Big Data and Brain Computing (BDBC), Beihang University, Beijing, China
4James D. Watson Institute of Genome Sciences, Hangzhou, China
5The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
6SKLSDE Lab, Beihang University, Beijing, China
7State 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
Yong Zhou, email: [email protected]
Min Yang, email: [email protected]
Xiaodong Fang, email: [email protected]
Jie Du, email: [email protected]
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
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.
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