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

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  • 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)

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.

Suggested Citation

  • 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 Aparici, 2014. "DNA barcoding reveals diverse growth kinetics of human breast tumour subclones in serially passaged xenografts," Nature Communications, Nature, vol. 5(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6871
    DOI: 10.1038/ncomms6871
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    Cited by:

    1. Humberto Contreras-Trujillo & Jiya Eerdeng & Samir Akre & Du Jiang & Jorge Contreras & Basia Gala & Mary C. Vergel-Rodriguez & Yeachan Lee & Aparna Jorapur & Areen Andreasian & Lisa Harton & Charles S, 2021. "Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Naomi Kawashima & Yuichi Ishikawa & Jeong Hui Kim & Yoko Ushijima & Akimi Akashi & Yohei Yamaguchi & Hikaru Hattori & Marie Nakashima & Seara Ikeno & Rika Kihara & Takahiro Nishiyama & Takanobu Morish, 2022. "Comparison of clonal architecture between primary and immunodeficient mouse-engrafted acute myeloid leukemia cells," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. F. Nadalin & M. J. Marzi & M. Pirra Piscazzi & P. Fuentes-Bravo & S. Procaccia & M. Climent & P. Bonetti & C. Rubolino & B. Giuliani & I. Papatheodorou & J. C. Marioni & F. Nicassio, 2024. "Multi-omic lineage tracing predicts the transcriptional, epigenetic and genetic determinants of cancer evolution," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    4. Peter Eirew & Ciara O’Flanagan & Jerome Ting & Sohrab Salehi & Jazmine Brimhall & Beixi Wang & Justina Biele & Teresa Algara & So Ra Lee & Corey Hoang & Damian Yap & Steven McKinney & Cherie Bates & E, 2022. "Accurate determination of CRISPR-mediated gene fitness in transplantable tumours," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    5. Qiuchen Guo & Milos Spasic & Adam G. Maynard & Gregory J. Goreczny & Amanuel Bizuayehu & Jessica F. Olive & Peter Galen & Sandra S. McAllister, 2022. "Clonal barcoding with qPCR detection enables live cell functional analyses for cancer research," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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