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

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, Xiaomei Zhang, Vandhana Ramamoorthy, Shirong Cai, Wenhui Wu, Giulio Draetta, Stacy L. Moulder, William F. Symmans, Jeffrey T. Chang, Timothy P. Heffernan and Helen Piwnica-Worms ()
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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
Zhongqi Ge: The University of Texas MD Anderson Cancer Center
Alessandro Carugo: The University of Texas MD Anderson Cancer Center
Christopher Bristow: The University of Texas MD Anderson Cancer Center
Michael Peoples: The University of Texas MD Anderson Cancer Center
Frederick Robinson: 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
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
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
Timothy P. Heffernan: The University of Texas MD Anderson Cancer Center
Helen Piwnica-Worms: The University of Texas MD Anderson Cancer Center

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07406-4

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