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

Long V. Nguyen, Claire L. Cox, Peter Eirew, David J. H. F. Knapp, Davide Pellacani, Nagarajan Kannan, Annaick Carles, Michelle Moksa, Sneha Balani, Sohrab Shah, Martin Hirst, Samuel Aparicio and Connie J. Eaves ()
Additional contact information
Long V. Nguyen: Terry Fox Laboratory, British Columbia Cancer Agency
Claire L. Cox: Terry Fox Laboratory, British Columbia Cancer Agency
Peter Eirew: British Columbia Cancer Agency
David J. H. F. Knapp: Terry Fox Laboratory, British Columbia Cancer Agency
Davide Pellacani: Terry Fox Laboratory, British Columbia Cancer Agency
Nagarajan Kannan: Terry Fox Laboratory, British Columbia Cancer Agency
Annaick Carles: Centre for High-Throughput Biology, University of British Columbia
Michelle Moksa: Centre for High-Throughput Biology, University of British Columbia
Sneha Balani: Terry Fox Laboratory, British Columbia Cancer Agency
Sohrab Shah: British Columbia Cancer Agency
Martin Hirst: Centre for High-Throughput Biology, University of British Columbia
Samuel Aparicio: British Columbia Cancer Agency
Connie J. Eaves: Terry Fox Laboratory, British Columbia Cancer Agency

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6871

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