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Preanalytical Variables for the Genomic Assessment of the Cellular and Acellular Fractions of the Liquid Biopsy in a Cohort of Breast Cancer Patients

Shishido, Stephanie N ; Welter, Lisa ; Rodriguez-Lee, Mariam ; Kolatkar, Anand ; Xu, Liya ; Ruiz, Carmen ; Gerdtsson, Anna S LU ; Restrepo-Vassalli, Sara ; Carlsson, Anders LU and Larsen, Joe , et al. (2020) In Journal of Molecular Diagnostics 22(3). p.319-337
Abstract

Liquid biopsy allows assessment of multiple analytes, providing temporal information with potential for improving understanding of cancer evolution and clinical management of patients. Although liquid biopsies are intensely investigated for prediction and response monitoring, preanalytic variables are of primary concern for clinical implementation, including categories of collection method and sample storage. Herein, an integrated high-density single-cell assay workflow for morphometric and genomic analysis of the liquid biopsy is used to characterize the effects of preanalytical variation and reproducibility of data from a breast cancer cohort. Following prior work quantifying performance of commonly used blood collection tubes, this... (More)

Liquid biopsy allows assessment of multiple analytes, providing temporal information with potential for improving understanding of cancer evolution and clinical management of patients. Although liquid biopsies are intensely investigated for prediction and response monitoring, preanalytic variables are of primary concern for clinical implementation, including categories of collection method and sample storage. Herein, an integrated high-density single-cell assay workflow for morphometric and genomic analysis of the liquid biopsy is used to characterize the effects of preanalytical variation and reproducibility of data from a breast cancer cohort. Following prior work quantifying performance of commonly used blood collection tubes, this study completes the analysis of four time points to assay (24, 48, 72, and 96 hours), demonstrating precision up to 48 hours after collection for assay sensitivity, highly reproducible rare cell enumeration, morphometric characterization, and high efficiency and capacity for single-cell genomic analysis. For the cell-free analysis, both freezing and use of fresh plasma produced similar quality and quantity of cell-free DNA for sequencing. The genomic analysis (copy number variation and single-nucleotide variation) described herein is broadly applicable to liquid biopsy platforms capable of isolating cell-free and cell-based DNA. Morphometric parameters and genomic signatures of individual circulating tumor cells were evaluated in relation to patient clinical response, providing preliminary evidence of clinical validity as a potential biomarker aiding clinical diagnostics or monitoring progression.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Molecular Diagnostics
volume
22
issue
3
pages
319 - 337
publisher
Elsevier
external identifiers
  • pmid:31978562
  • scopus:85080934953
ISSN
1525-1578
DOI
10.1016/j.jmoldx.2019.11.006
language
English
LU publication?
no
additional info
Copyright © 2020 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.
id
9b30fb05-2c06-4eb9-8516-5b02b962f740
date added to LUP
2020-03-09 12:39:36
date last changed
2024-09-19 18:24:50
@article{9b30fb05-2c06-4eb9-8516-5b02b962f740,
  abstract     = {{<p>Liquid biopsy allows assessment of multiple analytes, providing temporal information with potential for improving understanding of cancer evolution and clinical management of patients. Although liquid biopsies are intensely investigated for prediction and response monitoring, preanalytic variables are of primary concern for clinical implementation, including categories of collection method and sample storage. Herein, an integrated high-density single-cell assay workflow for morphometric and genomic analysis of the liquid biopsy is used to characterize the effects of preanalytical variation and reproducibility of data from a breast cancer cohort. Following prior work quantifying performance of commonly used blood collection tubes, this study completes the analysis of four time points to assay (24, 48, 72, and 96 hours), demonstrating precision up to 48 hours after collection for assay sensitivity, highly reproducible rare cell enumeration, morphometric characterization, and high efficiency and capacity for single-cell genomic analysis. For the cell-free analysis, both freezing and use of fresh plasma produced similar quality and quantity of cell-free DNA for sequencing. The genomic analysis (copy number variation and single-nucleotide variation) described herein is broadly applicable to liquid biopsy platforms capable of isolating cell-free and cell-based DNA. Morphometric parameters and genomic signatures of individual circulating tumor cells were evaluated in relation to patient clinical response, providing preliminary evidence of clinical validity as a potential biomarker aiding clinical diagnostics or monitoring progression.</p>}},
  author       = {{Shishido, Stephanie N and Welter, Lisa and Rodriguez-Lee, Mariam and Kolatkar, Anand and Xu, Liya and Ruiz, Carmen and Gerdtsson, Anna S and Restrepo-Vassalli, Sara and Carlsson, Anders and Larsen, Joe and Greenspan, Emily J and Hwang, E Shelley and Waitman, Kathryn R and Nieva, Jorge and Bethel, Kelly and Hicks, James and Kuhn, Peter}},
  issn         = {{1525-1578}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{319--337}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Molecular Diagnostics}},
  title        = {{Preanalytical Variables for the Genomic Assessment of the Cellular and Acellular Fractions of the Liquid Biopsy in a Cohort of Breast Cancer Patients}},
  url          = {{http://dx.doi.org/10.1016/j.jmoldx.2019.11.006}},
  doi          = {{10.1016/j.jmoldx.2019.11.006}},
  volume       = {{22}},
  year         = {{2020}},
}