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
Couturier, Dominique-Laurent
An, Angela
Vijayaraghavan, Aadhitthya
Hosking, Karen
Publication Date
2022-08-08Journal 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
PDX models, circulating tumour DNA, copy number aberrations, liquid biopsies, preclinical treatment study, Animals, Biomarkers, Tumor, Circulating Tumor DNA, Cost of Illness, Heterografts, Mice, Neoplasms
Sponsorship
Cancer Research UK (A25117)
Cancer Research UK (A22905)
National Institute for Health Research (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/
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: support@repository.cam.ac.uk