Journal Article

Comprehensive profiling of 1015 patients’ exomes reveals genomic-clinical associations in colorectal cancer

Zhao, Qi, Jing, Ying, Mai, Zong-Jiong, Zeng, Zhao-Lei, Pu, Heng-Ying, Ding, Pei-Rong, Jiang, Teng-Jia, Wu, Chen-Yi, Zhang, Jing, Wang, Ying-Nan, Huang, You-Sheng, Wang, Zi-Xian, Huang, Tanxiao, Li, Yu-Hong, Wu, Qi-Nian, Lu, Zheng-Hai, Chen, Shifu, Chen, Gong, Xu, Mingyan, Xu, Rui-Hua, Yao, Yi-Chen, Wang, Feng, Zhang, Xiaoni, He, Ming-Ming, Luo, Hui-Yan, Jia, Wei-Hua, Pan, Zhi-Zhong, Li, Li-Ren, Long, Renwen, Qiu, Miao-Zheng, Zhang, Dong-Shen, Chen, Yan-Xing

2022

Overview

The genetic basis of colorectal cancer (CRC) and its clinical associations remain poorly understood due to limited samples or targeted genes in current studies. Here, we perform ultradeep whole-exome sequencing on 1015 patients with CRC as part of the ChangKang Project. We identify 46 high-confident significantly mutated genes, 8 of which mutate in 14.9% of patients: LYST , DAPK1 , CR2 , KIF16B , NPIPB15 , SYTL2 , ZNF91 , and KIAA0586 . With an unsupervised clustering algorithm, we propose a subtyping strategy that classisfies CRC patients into four genomic subtypes with distinct clinical characteristics, including hypermutated, chromosome instability with high risk, chromosome instability with low risk, and genome stability. Analysis of immunogenicity uncover the association of immunogenicity reduction with genomic subtypes and poor prognosis in CRC. Moreover, we find that mitochondrial DNA copy number is an independent factor for predicting the survival outcome of CRCs. Overall, our results provide CRC-related molecular features for clinical practice and a valuable resource for translational research. The ChangKang (Heathy Bowel) project was established to collect molecular and clinical information of a thousand Chinese colorectal cancer patients. Here, the authors present the genomic landscape of the ChangKang cohort and find a subgroup of patients defined by abnormal mitochondrial copy numbers.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45 / 45/23 / 631/208/69 / 631/67/1857 / 631/67/2329 / 692/4028/67/69 / 692/699/67/1504/1885 / Algorithms / Cancer / Chromosomal Instability / Chromosomes / Clustering / Colorectal cancer / Colorectal Neoplasms - genetics / Copy number / Death-associated protein kinase / Exome - genetics / Genes / Genomics / Humanities and Social Sciences / Humans / Immunogenicity / Kinesins / Medical prognosis / Mitochondrial DNA / multidisciplinary / Patients / Science / Science (multidisciplinary) / Stability analysis / Subgroups / Whole Exome Sequencing - methods