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dc.contributor.authorCresswell, GD
dc.contributor.authorNichol, D
dc.contributor.authorSpiteri, I
dc.contributor.authorTari, H
dc.contributor.authorZapata, L
dc.contributor.authorHeide, T
dc.contributor.authorMaley, CC
dc.contributor.authorMagnani, L
dc.contributor.authorSchiavon, G
dc.contributor.authorAshworth, A
dc.contributor.authorBarry, P
dc.contributor.authorSottoriva, A
dc.date.accessioned2020-04-01T10:31:02Z
dc.date.issued2020-03-27
dc.identifier.citationNature communications, 2020, 11 (1), pp. 1446 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3565
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/s41467-020-15047-9
dc.description.abstractCirculating tumour DNA (ctDNA) allows tracking of the evolution of human cancers at high resolution, overcoming many limitations of tissue biopsies. However, exploiting ctDNA to determine how a patient's cancer is evolving in order to aid clinical decisions remains difficult. This is because ctDNA is a mix of fragmented alleles, and the contribution of different cancer deposits to ctDNA is largely unknown. Profiling ctDNA almost invariably requires prior knowledge of what genomic alterations to track. Here, we leverage on a rapid autopsy programme to demonstrate that unbiased genomic characterisation of several metastatic sites and concomitant ctDNA profiling at whole-genome resolution reveals the extent to which ctDNA is representative of widespread disease. We also present a methylation profiling method that allows tracking evolutionary changes in ctDNA at single-molecule resolution without prior knowledge. These results have critical implications for the use of liquid biopsies to monitor cancer evolution in humans and guide treatment.
dc.formatElectronic
dc.format.extent1446 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectClone Cells
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectNeoplasm Metastasis
dc.subjectDNA Methylation
dc.subjectEpigenesis, Genetic
dc.subjectDrug Resistance, Neoplasm
dc.subjectGenome, Human
dc.subjectFemale
dc.subjectClonal Evolution
dc.subjectCirculating Tumor DNA
dc.titleMapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking.
dc.typeJournal Article
dcterms.dateAccepted2020-02-18
rioxxterms.versionofrecord10.1038/s41467-020-15047-9
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-03-27
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.issue1
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.organisational-group/ICR/Students/PhD and MPhil/17/18 Starting Cohort
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.organisational-group/ICR/Students/PhD and MPhil/17/18 Starting Cohort
pubs.publication-statusPublished
pubs.volume11
pubs.embargo.termsNo embargo
icr.researchteamEvolutionary Genomics & Modellingen_US
dc.contributor.icrauthorHeide, Timonen
dc.contributor.icrauthorSpiteri Sagastume, Mariaen
dc.contributor.icrauthorTari, Haideren
dc.contributor.icrauthorSottoriva, Andreaen


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