Research

Single-cell sequencing deciphers a convergent evolution of copy number alterations from primary to circulating tumor cells

    • 1Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China;
    • 2Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA;
    • 3Department of Cancer Cell Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China;
    • 4Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China;
    • 5Department of Gastrointestinal Oncology,
    • 6Department of Breast Oncology,
    • 7Department of Interventional Therapy,
    • 8Department of Urologic Oncology,
    • 9Department of Breast Reconstruction, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China;
    • 10Pharmacological Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
    • 11 These authors contributed equally to this work.
Published May 9, 2017. Vol 27 Issue 8, pp. 1312-1322. https://doi.org/10.1101/gr.216788.116
Download PDF Please log-in to or register for your personal account in order to access PDF Cite Article Permissions Share
cover of Genome Research Vol 36 Issue 4
Current Issue:
April 2026, Vol. 36, No. 4
Focus view

Abstract

Copy number alteration (CNA) is a major contributor to genome instability, a hallmark of cancer. Here, we studied genomic alterations in single primary tumor cells and circulating tumor cells (CTCs) from the same patient. Single-nucleotide variants (SNVs) in single cells from both samples occurred sporadically, whereas CNAs among primary tumor cells emerged accumulatively rather than abruptly, converging toward the CNA in CTCs. Focal CNAs affecting the MYC gene and the PTEN gene were observed only in a minor portion of primary tumor cells but were present in all CTCs, suggesting a strong selection toward metastasis. Single-cell structural variant (SV) analyses revealed a two-step mechanism, a complex rearrangement followed by gene amplification, for the simultaneous formation of anomalous CNAs in multiple chromosome regions. Integrative CNA analyses of 97 CTCs from 23 patients confirmed the convergence of CNAs and revealed single, concurrent, and mutually exclusive CNAs that could be the driving events in cancer metastasis.

Back to top
Article contents

Announcement(s)