Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/20639
Title: Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer.
Authors: Merino, Delphine;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
Affiliation: ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia
Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, 1066 CX, The Netherlands
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Bundoora, VIC, 3086, Australia
Department of Medical Oncology, The Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia
Department of Medicine, The University of Melbourne, Melbourne, VIC, 3010, Australia
Parkville Familial Cancer Centre, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Parkville, VIC, 3050, Australia
Department of Medical Biology, The University of Melbourne, Melbourne, VIC, 3010, Australia
Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia
School of Mathematics and Statistics, The University of Melbourne, Melbourne, VIC, 3010, Australia
Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, 3010, Australia
Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia
Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia
Department of Medical Biology, The University of Melbourne, Melbourne, VIC, 3010, Australia
Issue Date: 15-Feb-2019
EDate: 2019-02-15
Citation: Nature communications 2019; 10(1): 766
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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/20639
DOI: 10.1038/s41467-019-08595-2
ORCID: 0000-0002-8075-6275
0000-0003-3836-3299
0000-0003-3229-3760
0000-0001-6187-819X
0000-0002-3684-4331
0000-0001-8366-9882
0000-0002-7579-0006
0000-0002-7872-6931
0000-0003-4911-5653
0000-0001-7082-6076
0000-0003-0517-8804
0000-0002-0951-7116
0000-0001-9221-2892
0000-0002-1102-8506
0000-0001-9386-2416
0000-0001-9173-6977
0000-0003-0299-3301
PubMed URL: 30770823
Type: Journal Article
Research Support, Non-U.S. Gov't
Appears in Collections:Journal articles

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