Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer

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dc.contributor.authorKreso, A.
dc.contributor.authorO'Brien, C.
dc.contributor.authorvan Galen, P.
dc.contributor.authorGan, O.
dc.contributor.authorNotta, F.
dc.contributor.authorBrown, A.
dc.contributor.authorNg, K.
dc.contributor.authorMa, J.
dc.contributor.authorWienholds, E.
dc.contributor.authorDunant, C.
dc.contributor.authorPollett, A.
dc.contributor.authorGallinger, S.
dc.contributor.authorMcPherson, J.
dc.contributor.authorMullighan, C.
dc.contributor.authorShibata, D.
dc.contributor.authorDick, J.
dc.date.issued2013
dc.description.abstractIntratumoral heterogeneity arises through the evolution of genetically diverse subclones during tumor progression. However, it remains unknown whether cells within single genetic clones are functionally equivalent. By combining DNA copy number alteration (CNA) profiling, sequencing, and lentiviral lineage tracking, we followed the repopulation dynamics of 150 single lentivirus-marked lineages from 10 human colorectal cancers through serial xenograft passages in mice. CNA and mutational analysis distinguished individual clones and showed that clones remained stable upon serial transplantation. Despite this stability, the proliferation, persistence, and chemotherapy tolerance of lentivirally marked lineages were variable within each clone. Chemotherapy promoted the dominance of previously minor or dormant lineages. Thus, apart from genetic diversity, tumor cells display inherent functional variability in tumor propagation potential, which contributes to both cancer growth and therapy tolerance.
dc.description.statementofresponsibilityAntonija Kreso, Catherine A. O’Brien, Peter van Galen, Olga I. Gan, Faiyaz Notta, Andrew M. K. Brown, Karen Ng, Jing Ma, Erno Wienholds, Cyrille Dunant, Aaron Pollett, Steven Gallinger, John McPherson, Charles G. Mullighan, Darryl Shibata, John E. Dick
dc.identifier.citationScienceAsia, 2013; 339(6119):543-548
dc.identifier.doi10.1126/science.1227670
dc.identifier.issn1513-1874
dc.identifier.issn1095-9203
dc.identifier.orcidMullighan, C. [0000-0002-1871-1850]
dc.identifier.urihttp://hdl.handle.net/2440/109317
dc.language.isoen
dc.publisherScience Society of Thailand
dc.rights2017 © The Authors, some rights reserved
dc.source.urihttps://doi.org/10.1126/science.1227670
dc.subjectClone Cells
dc.subjectTumor Cells, Cultured
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectLentivirus
dc.subjectColorectal Neoplasms
dc.subjectTransduction, Genetic
dc.subjectNeoplasm Transplantation
dc.subjectCell Lineage
dc.subjectDrug Resistance, Neoplasm
dc.subjectDNA Copy Number Variations
dc.subjectCell Tracking
dc.subjectTranscriptome
dc.subjectClonal Evolution
dc.titleVariable clonal repopulation dynamics influence chemotherapy response in colorectal cancer
dc.typeJournal article
pubs.publication-statusPublished

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