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dc.contributor.authorSottoriva, Aen_US
dc.contributor.authorKang, Hen_US
dc.contributor.authorMa, Zen_US
dc.contributor.authorGraham, TAen_US
dc.contributor.authorSalomon, MPen_US
dc.contributor.authorZhao, Jen_US
dc.contributor.authorMarjoram, Pen_US
dc.contributor.authorSiegmund, Ken_US
dc.contributor.authorPress, MFen_US
dc.contributor.authorShibata, Den_US
dc.contributor.authorCurtis, Cen_US
dc.date.accessioned2018-11-19T12:06:03Z
dc.date.issued2015-03en_US
dc.identifier.citationNature genetics, 2015, 47 (3), pp. 209 - 216en_US
dc.identifier.issn1061-4036en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2942
dc.identifier.eissn1546-1718en_US
dc.identifier.doi10.1038/ng.3214en_US
dc.description.abstractWhat happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion producing numerous intermixed subclones that are not subject to stringent selection and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors showed an absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear 'born to be bad', with subclone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH, with important clinical implications.en_US
dc.formatPrint-Electronicen_US
dc.format.extent209 - 216en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.subjectHumansen_US
dc.subjectColorectal Neoplasmsen_US
dc.subjectCell Growth Processesen_US
dc.subjectGenetic Heterogeneityen_US
dc.subjectModels, Biologicalen_US
dc.subjectModels, Geneticen_US
dc.titleA Big Bang model of human colorectal tumor growth.en_US
dc.typeJournal Article
dcterms.dateAccepted2015-01-12en_US
rioxxterms.versionofrecord10.1038/ng.3214en_US
rioxxterms.licenseref.startdate2015-03en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNature geneticsen_US
pubs.issue3en_US
pubs.notes6 monthsen_US
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.volume47en_US
pubs.embargo.terms6 monthsen_US
icr.researchteamEvolutionary Genomics & Modellingen_US
dc.contributor.icrauthorSottoriva, Andreaen_US


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