Childs, A;
Steele, CD;
Vesely, C;
Rizzo, FMM;
Ensell, L;
Lowe, H;
Dhami, P;
... Meyer, T; + view all
(2021)
Whole genome sequencing of single circulating tumor cells from neuroendocrine neoplasms.
Endocrine-Related Cancer
10.1530/ERC-21-0179.
(In press).
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[14796821 - Endocrine-Related Cancer] Whole genome sequencing of single circulating tumor cells from neuroendocrine neoplasms.pdf - Published Version Download (2MB) | Preview |
Abstract
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 demonstrate the presence of genomically distinct CTCs according to the enrichment strategy utilized (EpCAM-dependent versus 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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