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Nat Commun. 2015 Nov 4;6:8760. doi: 10.1038/ncomms9760.

Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer.

Author information

1
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
2
Department of Oncology, University of Cambridge, Cambridge CB2 0RE, UK.
3
Center for Noninvasive Diagnostics, Translational Genomics Research Institute, Phoenix, Arizona 85004, USA.
4
Mayo Clinic Center for Individualized Medicine, Scottsdale, Arizona 85259, USA.
5
Cambridge Breast Unit, Addenbrooke's Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research Centre, and the Cambridge Experimental Cancer Medicine Centre, Cambridge CB2 0QQ, UK.
6
Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.
7
Department of Histopathology, Addenbrooke's Hospital, Cambridge University Hospital NHS Foundation Trust, Cambridge CB2 0QQ, UK.
8
BC Cancer Research Centre, Vancouver, British Columbia, Canada V5Z 1L3.
9
Illumina, Inc., Chesterford Research Park, Little Chesterford CB10 1XL, UK.
10
Department of Radiology, Addenbrooke's Hospital, Cambridge University Hospital NHS Foundation Trust, Cambridge CB2 0QQ, UK.

Abstract

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.

PMID:
26530965
PMCID:
PMC4659935
DOI:
10.1038/ncomms9760
[Indexed for MEDLINE]
Free PMC Article

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