CUED Publications database

Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer.

Kreso, A and O'Brien, CA and van Galen, P and Gan, OI and Notta, F and Brown, AMK and Ng, K and Ma, J and Wienholds, E and Dunant, C and Pollett, A and Gallinger, S and McPherson, J and Mullighan, CG and Shibata, D and Dick, JE (2013) Variable clonal repopulation dynamics influence chemotherapy response in colorectal cancer. Science, 339. pp. 543-548.

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Intratumoral 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.

Item Type: Article
Uncontrolled Keywords: Animals Cell Lineage Cell Tracking Clonal Evolution Clone Cells Colorectal Neoplasms DNA Copy Number Variations Drug Resistance, Neoplasm Humans Lentivirus Mice Neoplasm Transplantation Transcriptome Transduction, Genetic Tumor Cells, Cultured
Divisions: Div D > Structures
Depositing User: Cron Job
Date Deposited: 17 Jul 2017 19:06
Last Modified: 22 Jun 2018 20:28