Longitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft models.
Authors
Belic, Jelena
Boyle, Samantha E
Hall, James A
An, Angela
Vijayaraghavan, Aadhitthya
Hosking, Karen
Publication Date
2022-06-13Journal Title
EMBO Mol Med
ISSN
1757-4676
Publisher
EMBO
Language
en
Type
Article
This Version
AO
VoR
Metadata
Show full item recordCitation
Sauer, C. M., Heider, K., Belic, J., Boyle, S. E., Hall, J. A., Couturier, D., An, A., et al. (2022). Longitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft models.. EMBO Mol Med https://doi.org/10.15252/emmm.202215729
Abstract
Whole-genome sequencing (WGS) of circulating tumour DNA (ctDNA) is now a clinically important biomarker for predicting therapy response, disease burden and disease progression. However, the translation of ctDNA monitoring into vital preclinical PDX models has not been possible owing to low circulating blood volumes in small rodents. Here, we describe the longitudinal detection and monitoring of ctDNA from minute volumes of blood in PDX mice. We developed a xenograft Tumour Fraction (xTF) metric using shallow WGS of dried blood spots (DBS), and demonstrate its application to quantify disease burden, monitor treatment response and predict disease outcome in a preclinical study of PDX mice. Further, we show how our DBS-based ctDNA assay can be used to detect gene-specific copy number changes and examine the copy number landscape over time. Use of sequential DBS ctDNA assays could transform future trial designs in both mice and patients by enabling increased sampling and molecular monitoring.
Keywords
EMBO03, Report, Reports, circulating tumour DNA, copy number aberrations, liquid biopsies, PDX models, preclinical treatment study
Sponsorship
Cancer Research UK (A25117)
Cancer Research UK (A22905)
National Institute for Health Research (NIHRDH-IS-BRC-1215-20014)
Identifiers
emmm202215729
External DOI: https://doi.org/10.15252/emmm.202215729
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338028
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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