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dc.contributor.authorBollen, Y
dc.contributor.authorStelloo, E
dc.contributor.authorvan Leenen, P
dc.contributor.authorvan den Bos, M
dc.contributor.authorPonsioen, B
dc.contributor.authorLu, B
dc.contributor.authorvan Roosmalen, MJ
dc.contributor.authorBolhaqueiro, ACF
dc.contributor.authorKimberley, C
dc.contributor.authorMossner, M
dc.contributor.authorCross, WCH
dc.contributor.authorBesselink, NJM
dc.contributor.authorvan der Roest, B
dc.contributor.authorBoymans, S
dc.contributor.authorOost, KC
dc.contributor.authorde Vries, SG
dc.contributor.authorRehmann, H
dc.contributor.authorCuppen, E
dc.contributor.authorLens, SMA
dc.contributor.authorKops, GJPL
dc.contributor.authorKloosterman, WP
dc.contributor.authorTerstappen, LWMM
dc.contributor.authorBarnes, CP
dc.contributor.authorSottoriva, A
dc.contributor.authorGraham, TA
dc.contributor.authorSnippert, HJG
dc.date.accessioned2021-09-21T13:35:29Z
dc.date.available2021-09-21T13:35:29Z
dc.identifier.citationNature genetics, 2021, 53 (8), pp. 1187 - 1195
dc.identifier.issn1061-4036
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4820
dc.identifier.eissn1546-1718
dc.identifier.doi10.1038/s41588-021-00891-2
dc.description.abstractCentral to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at single-cell resolution. Here, we present 3D Live-Seq-a protocol that integrates live-cell imaging of tumor organoid outgrowth and whole-genome sequencing of each imaged cell to reconstruct evolving tumor cell karyotypes across consecutive cell generations. Using patient-derived colorectal cancer organoids and fresh tumor biopsies, we demonstrate that karyotype alterations of varying complexity are prevalent and can arise within a few cell generations. Sub-chromosomal acentric fragments were prone to replication and collective missegregation across consecutive cell divisions. In contrast, gross genome-wide karyotype alterations were generated in a single erroneous cell division, providing support that aneuploid tumor genomes can evolve via punctuated evolution. Mapping the temporal dynamics and patterns of karyotype diversification in cancer enables reconstructions of evolutionary paths to malignant fitness.
dc.formatPrint-Electronic
dc.format.extent1187 - 1195
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectOrganoids
dc.subjectChromosomes, Human
dc.subjectChromatin
dc.subjectHumans
dc.subjectColorectal Neoplasms
dc.subjectMicroscopy, Confocal
dc.subjectKaryotyping
dc.subjectMitosis
dc.subjectCell Proliferation
dc.subjectGene Dosage
dc.subjectSingle-Cell Analysis
dc.subjectKaryotype
dc.subjectSpindle Apparatus
dc.titleReconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns.
dc.typeJournal Article
dcterms.dateAccepted2021-05-24
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41588-021-00891-2
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature genetics
pubs.issue8
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.publication-statusPublished
pubs.volume53
pubs.embargo.termsNot known
dc.contributor.icrauthorSottoriva, Andreaen


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