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

D. Merino (), T. S. Weber, A. Serrano, F. Vaillant, K. Liu, B. Pal, L. 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 () and S. H. Naik ()
Additional contact information
D. Merino: The Walter and Eliza Hall Institute of Medical Research
T. S. Weber: The University of Melbourne
A. Serrano: The Walter and Eliza Hall Institute of Medical Research
F. Vaillant: The Walter and Eliza Hall Institute of Medical Research
K. Liu: The Walter and Eliza Hall Institute of Medical Research
B. Pal: The Walter and Eliza Hall Institute of Medical Research
L. Stefano: The Walter and Eliza Hall Institute of Medical Research
J. Schreuder: The University of Melbourne
D. Lin: The University of Melbourne
Y. Chen: The University of Melbourne
M. L. Asselin-Labat: The Walter and Eliza Hall Institute of Medical Research
T. N. Schumacher: Netherlands Cancer Institute
D. Cameron: The Walter and Eliza Hall Institute of Medical Research
G. K. Smyth: The Walter and Eliza Hall Institute of Medical Research
A. T. Papenfuss: The University of Melbourne
G. J. Lindeman: The Walter and Eliza Hall Institute of Medical Research
J. E. Visvader: The Walter and Eliza Hall Institute of Medical Research
S. H. Naik: The University of Melbourne

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (7)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-08595-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08595-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-08595-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().