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    Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer

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    Author
    Merino, D; Weber, TS; Serrano, A; Vaillant, F; Liu, K; Pal, B; Di Stefano, L; Schreuder, J; Lin, D; Chen, Y; ...
    Date
    2019-02-15
    Source Title
    Nature Communications
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Smyth, Gordon; Asselin-Labat, Marie-Liesse; Papenfuss, Anthony; Vaillant, Francois; Visvader, Jane; Pal, Bhupinder; Lindeman, Geoffrey; Merino, Delphine; Naik, Shalin; Cameron, Daniel; ...
    Affiliation
    Medical Biology (W.E.H.I.)
    School of Mathematics and Statistics
    Medicine and Radiology
    Metadata
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    Document Type
    Journal Article
    Citations
    Merino, D., Weber, T. S., Serrano, A., Vaillant, F., Liu, K., Pal, B., Di Stefano, L., Schreuder, J., Lin, D., Chen, Y., Asselin-Labat, M. L., Schumacher, T. N., Cameron, D., Smyth, G. K., Papenfuss, A. T., Lindeman, G. J., Visvader, J. E. & Naik, S. H. (2019). Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer. NATURE COMMUNICATIONS, 10 (1), https://doi.org/10.1038/s41467-019-08595-2.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/253808
    DOI
    10.1038/s41467-019-08595-2
    Abstract
    Primary triple negative breast cancers (TNBC) are prone to dissemination but sub-clonal relationships between tumors and resulting metastases are poorly understood. Here we use cellular barcoding of two treatment-naïve TNBC patient-derived xenografts (PDXs) to track the spatio-temporal fate of thousands of barcoded clones in primary tumors, and their metastases. Tumor resection had a major impact on reducing clonal diversity in secondary sites, indicating that most disseminated tumor cells lacked the capacity to 'seed', hence originated from 'shedders' that did not persist. The few clones that continued to grow after resection i.e. 'seeders', did not correlate in frequency with their parental clones in primary tumors. Cisplatin treatment of one BRCA1-mutated PDX model to non-palpable levels had a surprisingly minor impact on clonal diversity in the relapsed tumor yet purged 50% of distal clones. Therefore, clonal features of shedding, seeding and drug resistance are important factors to consider for the design of therapeutic strategies.

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