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High-resolution clonal mapping of multi-organ metastasis in triple negative breast cancer

Author

Listed:
  • Gloria V. Echeverria

    (The University of Texas MD Anderson Cancer Center)

  • Emily Powell

    (The University of Texas MD Anderson Cancer Center)

  • Sahil Seth

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Zhongqi Ge

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Alessandro Carugo

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Christopher Bristow

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Michael Peoples

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Frederick Robinson

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Huan Qiu

    (The University of Texas Health Science Center)

  • Jiansu Shao

    (The University of Texas MD Anderson Cancer Center)

  • Sabrina L. Jeter-Jones

    (The University of Texas MD Anderson Cancer Center)

  • Xiaomei Zhang

    (The University of Texas MD Anderson Cancer Center)

  • Vandhana Ramamoorthy

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Shirong Cai

    (The University of Texas MD Anderson Cancer Center)

  • Wenhui Wu

    (The University of Texas MD Anderson Cancer Center)

  • Giulio Draetta

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Stacy L. Moulder

    (The University of Texas MD Anderson Cancer Center)

  • William F. Symmans

    (The University of Texas MD Anderson Cancer Center)

  • Jeffrey T. Chang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas Health Science Center)

  • Timothy P. Heffernan

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Helen Piwnica-Worms

    (The University of Texas MD Anderson Cancer Center)

Abstract

Most triple negative breast cancers (TNBCs) are aggressively metastatic with a high degree of intra-tumoral heterogeneity (ITH), but how ITH contributes to metastasis is unclear. Here, clonal dynamics during metastasis were studied in vivo using two patient-derived xenograft (PDX) models established from the treatment-naive primary breast tumors of TNBC patients diagnosed with synchronous metastasis. Genomic sequencing and high-complexity barcode-mediated clonal tracking reveal robust alterations in clonal architecture between primary tumors and corresponding metastases. Polyclonal seeding and maintenance of heterogeneous populations of low-abundance subclones is observed in each metastasis. However, lung, liver, and brain metastases are enriched for an identical population of high-abundance subclones, demonstrating that primary tumor clones harbor properties enabling them to seed and thrive in multiple organ sites. Further, clones that dominate multi-organ metastases share a genomic lineage. Thus, intrinsic properties of rare primary tumor subclones enable the seeding and colonization of metastases in secondary organs in these models.

Suggested Citation

  • Gloria V. Echeverria & Emily Powell & Sahil Seth & Zhongqi Ge & Alessandro Carugo & Christopher Bristow & Michael Peoples & Frederick Robinson & Huan Qiu & Jiansu Shao & Sabrina L. Jeter-Jones & Xiaom, 2018. "High-resolution clonal mapping of multi-organ metastasis in triple negative breast cancer," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07406-4
    DOI: 10.1038/s41467-018-07406-4
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    Cited by:

    1. Louise A. Baldwin & Nenad Bartonicek & Jessica Yang & Sunny Z. Wu & Niantao Deng & Daniel L. Roden & Chia-Ling Chan & Ghamdan Al-Eryani & Damien J. Zanker & Belinda S. Parker & Alexander Swarbrick & S, 2022. "DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and immunotherapy response," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. 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.

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