1. Single-cell exome sequencing reveals multiple subclones in metastatic colorectal carcinoma
- Author
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Lei Wang, Xin yi Ge, Dan Xie, Jie Tang, Kailing Tu, Xiaoling Liu, Keying Lu, Kai Luo, Guibo Li, Haoxuan Jin, Qilin Zhang, Lie Yang, Jiaxun Zhang, Zong-Guang Zhou, and Weiran Xiao
- Subjects
Male ,Colorectal cancer ,Cell ,QH426-470 ,Biology ,Metastatic tumours ,Metastasis ,Cell Movement ,Cell Line, Tumor ,Rare mutations ,Exome Sequencing ,Genetics ,medicine ,Humans ,Exome ,Neoplasm Metastasis ,Molecular Biology ,Gene ,Genetics (clinical) ,Exome sequencing ,Phylogeny ,Aged ,Research ,Liver Neoplasms ,Genomics ,Middle Aged ,medicine.disease ,Human genetics ,medicine.anatomical_structure ,Colorectal cancer, Single-cell DNA sequencing, Tumour metastasis ,Mutation ,Cancer research ,Medicine ,Molecular Medicine ,Female ,Single-Cell Analysis ,Colorectal Neoplasms - Abstract
BackgroundColorectal cancer (CRC) is a major cancer type whose mechanism of metastasis remains elusive.MethodsIn 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.ResultsDespite 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.ConclusionsIn 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.
- Published
- 2020