Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
- Department of Nuclear Medicine, University College London Hospitals, 235 Euston Road, Fitzrovia, London, NW1 2BU, UK.
- Advanced Sequencing Facility, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
- Department of Oncology, University College London Hospitals, 250 Euston Road, London NW1 2BU, UK.
- Department of Pathology, University College London Hospitals, 21 University Street, London WC1 6JJ, UK.
- Department of Cardiothoracic Surgery, University College London Hospitals, 235 Euston Road, Fitzrovia, London NW1 2BU, UK.
- Department of Respiratory Medicine, University College London Hospitals, 235 Euston Road, Fitzrovia, London NW1 2BU, UK.
- Department of Radiology, University College London Hospitals, 235 Euston Road, Fitzrovia, London NW1 2BU, UK.
- University of Manchester
- The Christie Hospital, Manchester M20 4BX, UK.
- Centre for Liver Research, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK.
- Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, UK.
- Natera Inc., 201 Industrial Road, San Carlos, California 94070, USA.
- University of Leicester
- Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
- Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
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.
|Number of pages||6|
|Early online date||26 Apr 2017|
|Publication status||Published - 25 May 2017|
- Non-small-cell lung cancer, Tumour heterogeneity, Metastasis , Diagnostic markers, Predictive markers