Journal
NATURE COMMUNICATIONS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms9760
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Funding
- NIHR Cambridge Biomedical Research Centre
- Cancer Research UK
- University of Cambridge, National Institute for Health Research Cambridge Biomedical Research Centre
- Cambridge Experimental Cancer Medicine Centre
- European Research Council under the European Union's Seventh Framework Programme (FP)/ERC Grant [337905]
- Australian National Breast Cancer Foundation
- Victorian Cancer Agency Early Career Fellowship
- Science Foundation Arizona's Bisgrove Scholars Early Tenure Track award
- MRC [MR/M008975/1] Funding Source: UKRI
- Academy of Medical Sciences (AMS) [AMS-SGCL11-Ali] Funding Source: researchfish
- Cancer Research UK [16942, 20240] Funding Source: researchfish
- Medical Research Council [MR/M008975/1] Funding Source: researchfish
- National Breast Cancer Foundation [ECF-14-027] Funding Source: researchfish
- National Institute for Health Research [CL-2013-14-006, NF-SI-0611-10154] Funding Source: researchfish
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Circulating tumour DNA analysis can be used to track tumour burden and analyse cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here we follow a patient with metastatic ER-positive and HER2-positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in eight tumour biopsies and nine plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing. Mutation levels in the plasma samples reflect the clonal hierarchy inferred from sequencing of tumour biopsies. Serial changes in circulating levels of sub-clonal private mutations correlate with different treatment responses between metastatic sites. This comparison of biopsy and plasma samples in a single patient with metastatic breast cancer shows that circulating tumour DNA can allow real-time sampling of multifocal clonal evolution.
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