Single-cell exome sequencing reveals multiple subclones in metastatic colorectal carcinoma

Genome Medicine

Guibo Li¹  Haoxuan Jin¹  Lei Wang¹  Zongguang Zhou²  Lie Yang²  Qilin Zhang³  Kai Luo³  Xin yi Ge³  Kailing Tu³  Dan Xie³  Jie Tang³  Xiaoling Liu³  Keying Lu³  Jiaxun Zhang³  Weiran Xiao³ 

[1]BGI-Shenzhen

[2]Department of Gastrointestinal Surgery, West China Hospital, Sichuan University

[3]National Frontier Center of Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University

关键词: Colorectal cancer, Single-cell DNA sequencing, Tumour metastasis;   

DOI  :  10.1186/s13073-021-00962-3

来源: DOAJ

【 摘 要 】

Abstract Background Colorectal cancer (CRC) is a major cancer type whose mechanism of metastasis remains elusive. Methods In this study, we characterised the evolutionary pattern of metastatic CRC (mCRC) by analysing bulk and single-cell exome sequencing data of primary and metastatic tumours from 7 CRC patients with liver metastases. Here, 7 CRC patients were analysed by bulk whole-exome sequencing (WES); 4 of these were also analysed using single-cell sequencing. Results Despite low genomic divergence between paired primary and metastatic cancers in the bulk data, single-cell WES (scWES) data revealed rare mutations and defined two separate cell populations, indicative of the diverse evolutionary trajectories between primary and metastatic tumour cells. We further identified 24 metastatic cell-specific-mutated genes and validated their functions in cell migration capacity. Conclusions In summary, scWES revealed rare mutations that failed to be detected by bulk WES. These rare mutations better define the distinct genomic profiles of primary and metastatic tumour cell clones.

【 授权许可】

Unknown