Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients
Open accessAbstract
Circulating tumor cells (CTCs) enter peripheral blood from primary tumors and seed metastases. The genome sequencing of CTCs could offer noninvasive prognosis or even diagnosis, but has been hampered by low single-cell genome coverage of scarce CTCs. Here, we report the use of the recently developed multiple annealing and looping-based amplification cycles for whole-genome amplification of single CTCs from lung cancer patients. We observed characteristic cancer-associated single-nucleotide variations and insertions/deletions in exomes of CTCs. These mutations provided information needed for individualized therapy, such as drug resistance and phenotypic transition, but were heterogeneous from cell to cell. In contrast, every CTC from an individual patient, regardless of the cancer subtypes, exhibited reproducible copy number variation (CNV) patterns, similar to those of the metastatic tumor of the same patient. Interestingly, different patients with the same lung cancer adenocarcinoma (ADC) shared similar CNV patterns in their CTCs. Even more interestingly, patients of small-cell lung cancer have CNV patterns distinctly different from those of ADC patients. Our finding suggests that CNVs at certain genomic loci are selected for the metastasis of cancer. The reproducibility of cancer-specific CNVs offers potential for CTC-based cancer diagnostics.
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A small needle biopsy of a single lesion may fail to reflect intra- and inter-tumor genetic heterogeneity.
“a small needle biopsy of a single lesion may fail to reflect the true underlying intra- and inter-tumor genetic heterogeneity (15–17).”
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- Authors
- Ni, X., Zhuo, M., Su, Z., Duan, J., Gao, Y., Wang, Z., Zong, C., Bai, H., Chapman, A. R., Zhao, J., Xu, L., An, T., Ma, Q., Wang, Y., Wu, M., Sun, Y., Wang, S., Li, Z., Yang, X., Yong, J., Su, X.-D., Lu, Y., Bai, F., Xie, X. S., & Wang, J.
- Affiliations
- Peking University (CN)
- Departments of cThoracic Medical Oncology and
- Department of Chemistry and Chemical Biology,
- Harvard University (US)
- Pathology,
- Biodynamic Optical Imaging Center, School of Life Sciences, Peking University, Beijing 100871, China;
- Peking University Cancer Hospital (CN)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-12-09
- Volume
- 110
- Issue
- 52
- Pages
- 21083-21088
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3876226
- OpenAlex
- W2008628868
- Cited by
- 454
- References
- 43
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 12 · 2023: 16 · 2022: 49 · 2021: 35 · 2020: 29 · 2019: 51 · 2018: 37 · 2017: 53 · 2016: 54 · 2015: 56 · 2014: 36
- FWCI
- 17.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- Peking University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- circulating tumor cells, lung cancer, copy number variation, single-cell DNA sequencing, whole genome amplification, single nucleotide variants, indels, metastasis, small cell lung cancer, lung adenocarcinoma, cellular heterogeneity, cancer diagnosis, drug resistance
- MeSH terms
- Base Sequence, Humans, Lung Neoplasms, Molecular Sequence Data, Neoplastic Cells, Circulating, Neoplasm Metastasis, Gene Library, Genome, Human, Cluster Analysis, Sequence Analysis, DNA, DNA Copy Number Variations, Pathology, Molecular, Precision Medicine, Exome
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