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dc.contributor.authorSauer, Carolin M
dc.contributor.authorHeider, Katrin
dc.contributor.authorBelic, Jelena
dc.contributor.authorBoyle, Samantha E
dc.contributor.authorHall, James A
dc.contributor.authorCouturier, Dominique
dc.contributor.authorAn, Angela
dc.contributor.authorVijayaraghavan, Aadhitthya
dc.contributor.authorReinius, Marika Av
dc.contributor.authorHosking, Karen
dc.contributor.authorVias Lopez, Maria
dc.contributor.authorRosenfeld, Nitzan
dc.contributor.authorBrenton, James
dc.date.accessioned2022-06-13T09:00:19Z
dc.date.available2022-06-13T09:00:19Z
dc.date.issued2022-08-08
dc.date.submitted2022-01-18
dc.identifier.issn1757-4676
dc.identifier.otheremmm202215729
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338028
dc.description.abstractWhole-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.
dc.languageen
dc.publisherEMBO
dc.subjectEMBO03
dc.subjectReport
dc.subjectReports
dc.subjectcirculating tumour DNA
dc.subjectcopy number aberrations
dc.subjectliquid biopsies
dc.subjectPDX models
dc.subjectpreclinical treatment study
dc.titleLongitudinal monitoring of disease burden and response using ctDNA from dried blood spots in xenograft models.
dc.typeArticle
dc.date.updated2022-06-13T09:00:18Z
prism.publicationNameEMBO Mol Med
dc.identifier.doi10.17863/CAM.85435
dcterms.dateAccepted2022-05-19
rioxxterms.versionofrecord10.15252/emmm.202215729
rioxxterms.versionAO
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidSauer, Carolin M [0000-0003-2168-6630]
dc.contributor.orcidHeider, Katrin [0000-0003-4035-1668]
dc.contributor.orcidCouturier, Dominique [0000-0001-5774-5036]
dc.contributor.orcidReinius, Marika Av [0000-0002-9778-3317]
dc.contributor.orcidVias Lopez, Maria [0000-0003-4955-0102]
dc.contributor.orcidRosenfeld, Nitzan [0000-0002-2825-4788]
dc.contributor.orcidBrenton, James [0000-0002-5738-6683]
dc.identifier.eissn1757-4684
pubs.funder-project-idCancer Research UK (A25117)
pubs.funder-project-idCancer Research UK (A22905)
pubs.funder-project-idNational Institute for Health Research (IS-BRC-1215-20014)
cam.issuedOnline2022-06-13


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