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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

D. Merino, T. S. Weber, A. Serrano, F. Vaillant, K. Liu, B. Pal, L. Di Stefano, J. Schreuder, D. Lin, Y. Chen, M. L. Asselin-Labat, T. N. Schumacher, D. Cameron, G. K. Smyth, A. T. Papenfuss, G. J. Lindeman, J. E. Visvader, S. H. Naik

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. More... »

PAGES

766

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-019-08595-2

    DOI

    http://dx.doi.org/10.1038/s41467-019-08595-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112165471

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30770823


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    445 schema:name Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands
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    447 https://www.grid.ac/institutes/grid.482637.c schema:alternateName Olivia Newton-John Cancer Wellness & Research Centre
    448 schema:name ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, 3052, Parkville, VIC, Australia
    449 Department of Medical Biology, The University of Melbourne, 3010, Melbourne, VIC, Australia
    450 Olivia Newton-John Cancer Research Institute, 3084, Heidelberg, VIC, Australia
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