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


Merino, D; Weber, TS; Serrano, A; Vaillant, F; Liu, K; Pal, B; Di Stefano, L; Schreuder, J; Lin, D; Chen, Y; Asselin-Labat, ML; Schumacher, TN; Cameron, D; Smyth, GK; Papenfuss, AT; Lindeman, GJ; Visvader, JE; Naik, SH
2019-02-15
Nature Communications
Journal Article
10
1
766
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-naive 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.
Springer Nature
Cancer Biology and Stem Cells; Bioinformatics; Immunology
10.1038/s41467-019-08595-2
30770823
Refer to article for additional funding acknowledgements
Refer to copyright notice on published article.

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Creation Date 2019-03-13 11:54:09 Last Modified 2019-03-13 02:01:03