Longitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft models
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...
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| Format: | Article |
| Language: | English |
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Springer Nature
2022-06-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202215729 |
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| author | Carolin M Sauer Katrin Heider Jelena Belic Samantha E Boyle James A Hall Dominique‐Laurent Couturier Angela An Aadhitthya Vijayaraghavan Marika AV Reinius Karen Hosking Maria Vias Nitzan Rosenfeld James D Brenton |
| author_facet | Carolin M Sauer Katrin Heider Jelena Belic Samantha E Boyle James A Hall Dominique‐Laurent Couturier Angela An Aadhitthya Vijayaraghavan Marika AV Reinius Karen Hosking Maria Vias Nitzan Rosenfeld James D Brenton |
| author_sort | Carolin M Sauer |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d7402f932e024ca29f08a4f9f317194b |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2022-06-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-d7402f932e024ca29f08a4f9f317194b2025-08-20T03:43:01ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842022-06-0114811210.15252/emmm.202215729Longitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft modelsCarolin M Sauer0Katrin Heider1Jelena Belic2Samantha E Boyle3James A Hall4Dominique‐Laurent Couturier5Angela An6Aadhitthya Vijayaraghavan7Marika AV Reinius8Karen Hosking9Maria Vias10Nitzan Rosenfeld11James D Brenton12Cancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Major Centre–Cambridge, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeAbstract 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.https://doi.org/10.15252/emmm.202215729circulating tumour DNAcopy number aberrationsliquid biopsiesPDX modelspreclinical treatment study |
| spellingShingle | Carolin M Sauer Katrin Heider Jelena Belic Samantha E Boyle James A Hall Dominique‐Laurent Couturier Angela An Aadhitthya Vijayaraghavan Marika AV Reinius Karen Hosking Maria Vias Nitzan Rosenfeld James D Brenton Longitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft models EMBO Molecular Medicine circulating tumour DNA copy number aberrations liquid biopsies PDX models preclinical treatment study |
| title | Longitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft models |
| title_full | Longitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft models |
| title_fullStr | Longitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft models |
| title_full_unstemmed | Longitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft models |
| title_short | Longitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft models |
| title_sort | longitudinal monitoring of disease burden and response using ctdna from dried blood spots in xenograft models |
| topic | circulating tumour DNA copy number aberrations liquid biopsies PDX models preclinical treatment study |
| url | https://doi.org/10.15252/emmm.202215729 |
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