Show simple item record

dc.contributor.authorSun, R
dc.contributor.authorHu, Z
dc.contributor.authorSottoriva, A
dc.contributor.authorGraham, TA
dc.contributor.authorHarpak, A
dc.contributor.authorMa, Z
dc.contributor.authorFischer, JM
dc.contributor.authorShibata, D
dc.contributor.authorCurtis, C
dc.date.accessioned2017-07-24T10:34:09Z
dc.date.issued2017-07
dc.identifier.citationNature genetics, 2017, 49 (7), pp. 1015 - 1024
dc.identifier.issn1061-4036
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/742
dc.identifier.eissn1546-1718
dc.identifier.doi10.1038/ng.3891
dc.description.abstractGiven the implications of tumor dynamics for precision medicine, there is a need to systematically characterize the mode of evolution across diverse solid tumor types. In particular, methods to infer the role of natural selection within established human tumors are lacking. By simulating spatial tumor growth under different evolutionary modes and examining patterns of between-region subclonal genetic divergence from multiregion sequencing (MRS) data, we demonstrate that it is feasible to distinguish tumors driven by strong positive subclonal selection from those evolving neutrally or under weak selection, as the latter fail to dramatically alter subclonal composition. We developed a classifier based on measures of between-region subclonal genetic divergence and projected patient data into model space, finding different modes of evolution both within and between solid tumor types. Our findings have broad implications for how human tumors progress, how they accumulate intratumoral heterogeneity, and ultimately how they may be more effectively treated.
dc.formatPrint-Electronic
dc.format.extent1015 - 1024
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectClone Cells
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectMice, Nude
dc.subjectAdenocarcinoma
dc.subjectColorectal Neoplasms
dc.subjectCocarcinogenesis
dc.subjectDisease Progression
dc.subjectDNA, Neoplasm
dc.subjectTumor Burden
dc.subjectEvolution, Molecular
dc.subjectCell Division
dc.subjectGene Frequency
dc.subjectMutation
dc.subjectAlleles
dc.subjectModels, Biological
dc.subjectTime Factors
dc.subjectComputer Simulation
dc.subjectMale
dc.subjectNeoplastic Stem Cells
dc.subjectGenetic Variation
dc.subjectSelection, Genetic
dc.subjectExome
dc.titleBetween-region genetic divergence reflects the mode and tempo of tumor evolution.
dc.typeJournal Article
dcterms.dateAccepted2017-05-05
rioxxterms.versionofrecord10.1038/ng.3891
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-07
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature genetics
pubs.issue7
pubs.notes6 months
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.publication-statusPublished
pubs.volume49
pubs.embargo.terms6 months
dc.contributor.icrauthorSottoriva, Andreaen


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record