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Nat Commun. 2014 Dec 23;5:5871. doi: 10.1038/ncomms6871.

DNA barcoding reveals diverse growth kinetics of human breast tumour subclones in serially passaged xenografts.

Author information

1
Terry Fox Laboratory, British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
2
Department of Molecular Oncology, British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.
3
Centre for High-Throughput Biology, Department of Microbiology &Immunology, University of British Columbia, 2125 East Mall, Vancouver, British Columbia, Canada V6T 1Z4.

Abstract

Genomic and phenotypic analyses indicate extensive intra- as well as intertumoral heterogeneity in primary human malignant cell populations despite their clonal origin. Cellular DNA barcoding offers a powerful and unbiased alternative to track the number and size of multiple subclones within a single human tumour xenograft and their response to continued in vivo passaging. Using this approach we find clone-initiating cell frequencies that vary from ~1/10 to ~1/10,000 cells transplanted for two human breast cancer cell lines and breast cancer xenografts derived from three different patients. For the cell lines, these frequencies are negatively affected in transplants of more than 20,000 cells. Serial transplants reveal five clonal growth patterns (unchanging, expanding, diminishing, fluctuating or of delayed onset), whose predominance is highly variable both between and within original samples. This study thus demonstrates the high growth potential and diverse growth properties of xenografted human breast cancer cells.

PMID:
25532760
PMCID:
PMC4284657
DOI:
10.1038/ncomms6871
[Indexed for MEDLINE]
Free PMC Article

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