title: Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients.
abstract: 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.
authors: Biodynamic Optical Imaging Center, School of Life Sciences, Peking University, Beijing 100871, China.
authors: Xiaohui
authors: X
authors: Ni
authors: Minglei
authors: M
authors: Zhuo
authors: Zhe
authors: Z
authors: Su
authors: Jianchun
authors: J
authors: Duan
authors: Yan
authors: Y
authors: Gao
authors: Zhijie
authors: Z
authors: Wang
authors: Chenghang
authors: C
authors: Zong
authors: Hua
authors: H
authors: Bai
authors: Alec R
authors: AR
authors: Chapman
authors: Jun
authors: J
authors: Zhao
authors: Liya
authors: L
authors: Xu
authors: Tongtong
authors: T
authors: An
authors: Qi
authors: Q
authors: Ma
authors: Yuyan
authors: Y
authors: Wang
authors: Meina
authors: M
authors: Wu
authors: Yu
authors: Y
authors: Sun
authors: Shuhang
authors: S
authors: Wang
authors: Zhenxiang
authors: Z
authors: Li
authors: Xiaodan
authors: X
authors: Yang
authors: Jun
authors: J
authors: Yong
authors: Xiao-Dong
authors: XD
authors: Su
authors: Youyong
authors: Y
authors: Lu
authors: Fan
authors: F
authors: Bai
authors: X Sunney
authors: XS
authors: Xie
authors: Jie
authors: J
authors: Wang
mesh_terms: D001483:Base Sequence; D016000:Cluster Analysis; D056915:DNA Copy Number Variations / Q000235:genetics*; D059472:Exome / Q000235:genetics; D015723:Gene Library; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000235:genetics*; D009360:Neoplastic Cells, Circulating / Q000737:chemistry*; D057089:Pathology, Molecular / Q000379:methods; D057285:Precision Medicine / Q000379:methods; D017422:Sequence Analysis, DNA
keywords: cancer diagnostics; personalized therapy