Journal
NATURE
Volume 545, Issue 7655, Pages 446-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/nature22364
Keywords
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Categories
Funding
- Francis Crick Institute - Cancer Research UK [FC001169, FC001202]
- UK Medical Research Council [FC001169, FC001202]
- Wellcome Trust [FC001169, FC001202]
- Cancer Research UK (TRACERx and CRUK Cancer Immunotherapy Catalyst Network)
- CRUK Lung Cancer Centre of Excellence
- Stand Up 2 Cancer (SU2C)
- Rosetrees Trust
- NovoNordisk Foundation [16584]
- Prostate Cancer Foundation
- Breast Cancer Research Foundation
- European Research Council (THESEUS)
- National Institute for Health Research
- University College London Hospitals Biomedical Research Centre
- Cancer Research UK University College London Experimental Cancer Medicine Centre
- University College London [UCL/12/0279, UCL/13/0165]
- Cancer Research UK [C11496/A17786, C416/A21999]
- Wellcome Trust [107963/Z/15/Z] Funding Source: Wellcome Trust
- Cancer Research UK [17786, 20274, 20465, 23896, 19310, 22246, 19278, 18176, 20466, 17891, 20275, 15954, 22795, 19740, 15951, 21999] Funding Source: researchfish
- Medical Research Council [MC_UP_1203/1, G108/596] Funding Source: researchfish
- National Institute for Health Research [CL-2015-18-009, CL-2015-17-002] Funding Source: researchfish
- Novo Nordisk Fonden [NNF15OC0016584] Funding Source: researchfish
- Rosetrees Trust [M510-CD1, M35-F1-CD1, M179, M630, M35-F2] Funding Source: researchfish
- The Francis Crick Institute [10202, C50947/A18176, 10169, 10002] Funding Source: researchfish
- Versus Arthritis
- Cancer Research UK [18892, 20613, 20265] Funding Source: researchfish
- Wellcome Trust [107963/Z/15/Z] Funding Source: researchfish
- MRC [MC_UP_1203/1, G108/596] Funding Source: UKRI
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The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.
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