4.7 Article

scDPN for High-throughput Single-cell CNV Detection to Uncover Clonal Evolution During HCC Recurrence

期刊

GENOMICS PROTEOMICS & BIOINFORMATICS
卷 19, 期 3, 页码 346-357

出版社

ELSEVIER
DOI: 10.1016/j.gpb.2021.03.008

关键词

Single-cell sequencing; Hepatocellular carcinoma; Heterogeneity; Clonal evolution; Relapse

资金

  1. Technology and Innovation Commission of Shenzhen Municipality, China [GJHZ20180419190827179]
  2. Science, Technology and Innovation Commission of Shenzhen Municipality, China [JCYJ20170303151334808]
  3. China National GeneBank

向作者/读者索取更多资源

The single-cell DNA library preparation method developed in this study, known as scDPN, eliminates the need for preamplification and allows for high-throughput CNV detection. It shows lower amplification bias and noise compared to the MDA method, and demonstrates high sensitivity and accuracy in evaluating cell lines and tumor tissues. Additionally, it was used to identify clonal subpopulations in hepatocellular carcinoma (HCC) samples, revealing clonal selection during tumor recurrence. Overall, this approach provides a comprehensive and scalable solution for understanding genome heterogeneity and evolution.
Single-cell genomics provides substantial resources for dissecting cellular heterogeneity and cancer evolution. Unfortunately, classical DNA amplification-based methods have low throughput and introduce coverage bias during sample preamplification. We developed a single-cell DNA library preparation method without preamplification in nanolitre scale (scDPN) to address these issues. The method achieved a throughput of up to 1800 cells per run for copy number variation (CNV) detection. Also, our approach demonstrated a lower level of amplification bias and noise than the multiple displacement amplification (MDA) method and showed high sensitivity and accuracy for cell line and tumor tissue evaluation. We used this approach to profile the tumor clones in paired primary and relapsed tumor samples of hepatocellular carcinoma (HCC). We identified three clonal subpopulations with a multitude of aneuploid alterations across the genome. Furthermore, we observed that a minor clone of the primary tumor containing additional alterations in chromosomes 1q, 10q, and 14q developed into the dominant clone in the recurrent tumor, indicating clonal selection during recurrence in HCC. Overall, this approach provides a comprehensive and scalable solution to understand genome heterogeneity and evolution.

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