4.4 Article

Whole-genome sequencing of single circulating tumor cells from neuroendocrine neoplasms

期刊

ENDOCRINE-RELATED CANCER
卷 28, 期 9, 页码 631-644

出版社

BIOSCIENTIFICA LTD
DOI: 10.1530/ERC-21-0179

关键词

neuroendocrine tumors; circulating tumor cells; single cell; copy number variation; whole-genome sequencing

资金

  1. CRUK
  2. EPSRC Comprehensive Cancer Imaging Center
  3. European Neuroendocrine Tumor Society Fellowship
  4. University College London (UCL) CRUK
  5. NIHR Experimental Cancer Medicine Center [C12125/A15576]
  6. MRC [MR/M009033/1]
  7. UCL Hospitals NIHR Biomedical Research Center
  8. MRC [MR/M009033/1] Funding Source: UKRI

向作者/读者索取更多资源

The study compared single-cell copy number variation (CNV) data of circulating tumor cells (CTCs) with tissue samples to define genomic heterogeneity, revealing recurrent chromosomal alterations and significant intra- and inter-patient genomic heterogeneity. This has implications for identifying therapeutic targets and implementing CTC-biomarkers in cancer.
Single-cell profiling of circulating tumor cells (CTCs) as part of a minimally invasive liquid biopsy presents an opportunity to characterize and monitor tumor heterogeneity and evolution in individual patients. In this study, we aimed to compare single-cell copy number variation (CNV) data with tissue and define the degree of intra- and inter-patient genomic heterogeneity. We performed next-generation sequencing (NGS) whole-genome CNV analysis of 125 single CTCs derived from seven patients with neuroendocrine neoplasms (NEN) alongside matched white blood cells (WBC), formalin-fixed paraffin-embedded (FFPE), and fresh frozen (FF) samples. CTC CNV profiling demonstrated recurrent chromosomal alterations in previously reported NEN copy number hotspots, including the prognostically relevant loss of chromosome 18. Unsupervised hierarchical clustering revealed CTCs with distinct clonal lineages as well as significant intra- and inter-patient genomic heterogeneity, including subclonal alterations not detectable by bulk analysis and previously unreported in NEN. Notably, we also demonstrated the presence of genomically distinct CTCs according to the enrichment strategy utilized (EpCAM-dependent vs size-based). This work has significant implications for the identification of therapeutic targets, tracking of evolutionary change, and the implementation of CTC-biomarkers in cancer.

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