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Updated: Oct 26, 2025
Target Cell Pre-enrichment and Whole Genome Amplification for Single Cell Downstream Characterization
Published on: May 15, 2018
Single-cell DNA methylome analysis of circulating tumor cells
Hengyu Chen1, Zhe Su1, Ruoyan Li1
1Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.
Objective:
Previous investigations of circulating tumor cells (CTCs) have mainly focused on their genomic or transcriptomic features, leaving their epigenetic landscape relatively uncharacterized. Here, we investigated the genome-wide DNA methylome of CTCs with a view to understanding the epigenetic regulatory mechanisms underlying cancer metastasis.
Methods:
We evaluated single-cell DNA methylome and copy number alteration (CNA) in 196 single cells, including 107 CTCs collected from 17 cancer patients covering six different cancer types. Our single-cell bisulfite sequencing (scBS-seq) covered on average 11.78% of all CpG dinucleotides and accurately deduced the CNA patterns at 500 kb resolution.
Results:
We report distinct subclonal structures and different evolutionary histories of CTCs inferred from CNA and DNA methylation profiles. Furthermore, we demonstrate potential tumor origin classification based on the tissue-specific DNA methylation profiles of CTCs.
Conclusions:
Our work provides a comprehensive survey of genome-wide DNA methylome in single CTCs and reveals 5-methylcytosine (5-mC) heterogeneity in CTCs, addressing the potential epigenetic regulatory mechanisms underlying cancer metastasis and facilitating the future clinical application of CTCs.
