Journal article

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

D Merino, TS Weber, A Serrano, F Vaillant, K Liu, B Pal, L Di Stefano, J Schreuder, D Lin, Y Chen, ML Asselin-Labat, TN Schumacher, D Cameron, GK Smyth, AT Papenfuss, GJ Lindeman, JE Visvader, SH Naik



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 parenta..

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Awarded by National Health and Medical Research Council, Australia (NHMRC)

Awarded by NHMRC

Funding Acknowledgements

We are grateful to M. Dawson for critical appraisal, D. Zalcenstein, J. Tran, and M. Ritchie for assistance, S. Wilcox and D. McCarthy for advice, the Royal Melbourne Hospital Tissue Bank, the Victorian Cancer Biobank, and the WEHI Animal, FACS and Histology facilities. This work was supported by the National Health and Medical Research Council, Australia (NHMRC, 1016701, 1040978, 1086727, 1124812, 1062820, 1145814, 1101378, and 1054618); NHMRC IRIISS; the Australian Cancer Research Foundation; The Joan Marshall Breast Cancer Research Fund. D.M. was supported by a NBCF Early Career Fellowship; M.L.A.L. by a Viertel Senior Medical Researcher Fellowship; G.K.S. by NHMRC Research Fellowship 1058892, A.T.P. by NHMRC Research Fellowship (1116955); G.J.L. by NHMRC Research Fellowship (1078730); J.E.V. by NHMRC Fellowships (1037230, 1102742).