Journal article

Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA

Muhammed Murtaza, Sarah-Jane Dawson, Dana WY Tsui, Davina Gale, Tim Forshew, Anna M Piskorz, Christine Parkinson, Suet-Feung Chin, Zoya Kingsbury, Alvin SC Wong, Francesco Marass, Sean Humphray, James Hadfield, David Bentley, Tan Min Chin, James D Brenton, Carlos Caldas, Nitzan Rosenfeld



Cancers acquire resistance to systemic treatment as a result of clonal evolution and selection. Repeat biopsies to study genomic evolution as a result of therapy are difficult, invasive and may be confounded by intra-tumour heterogeneity. Recent studies have shown that genomic alterations in solid cancers can be characterized by massively parallel sequencing of circulating cell-free tumour DNA released from cancer cells into plasma, representing a non-invasive liquid biopsy. Here we report sequencing of cancer exomes in serial plasma samples to track genomic evolution of metastatic cancers in response to therapy. Six patients with advanced breast, ovarian and lung cancers were followed over ..

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Awarded by Cancer Research UK

Awarded by National Institute for Health Research

Funding Acknowledgements

We thank J. Langmore and K. Solomon (Rubicon Genomics) for early access to library preparation products. We thank L. Jones, S. Richardson, C. Hodgkin and H. Biggs for recruiting patients into the DETECT and CTCR-OVO4 studies, all medical and ancillary staff in the breast and gynaecological cancer clinic and patients for consenting to participate. We thank the Human Research Tissue Bank at Addenbrooke's Hospital which is supported by the NIHR Cambridge Biomedical Research Centre. We thank the Cancer Science Institute, National University of Singapore, and the Hematology-Oncology Research Group, National University Health System, Singapore for their support. We acknowledge the support of Cancer Research UK, the University of Cambridge, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa Limited, and the National Medical Research Council, Singapore. S.-J.D. is supported by an Australian NHMRC/RG Menzies Early Career Fellowship that is administered through the Peter MacCallum Cancer Centre, Victoria, Australia.