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


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.

SUBMITTER: Tang J 

PROVIDER: S-EPMC8434739 | biostudies-literature |

REPOSITORIES: biostudies-literature

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