Publication Date:
2012-12-15
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kreso, Antonija -- O'Brien, Catherine A -- van Galen, Peter -- Gan, Olga I -- Notta, Faiyaz -- Brown, Andrew M K -- Ng, Karen -- Ma, Jing -- Wienholds, Erno -- Dunant, Cyrille -- Pollett, Aaron -- Gallinger, Steven -- McPherson, John -- Mullighan, Charles G -- Shibata, Darryl -- Dick, John E -- R21 CA149990/CA/NCI NIH HHS/ -- R21CA149990-01/CA/NCI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2013 Feb 1;339(6119):543-8. doi: 10.1126/science.1227670. Epub 2012 Dec 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Campbell Family Institute, Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23239622" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Lineage
;
Cell Tracking
;
Clonal Evolution/*genetics
;
Clone Cells
;
Colorectal Neoplasms/*drug therapy/genetics/*pathology
;
DNA Copy Number Variations
;
Drug Resistance, Neoplasm/*genetics
;
Humans
;
Lentivirus
;
Mice
;
Neoplasm Transplantation
;
Transcriptome
;
Transduction, Genetic
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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