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PMID: 28445469 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

Nature ·Vol. 545 ·No. 7655 ·2017-00-26 ·页码 446-451

Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, Le Quesne J, Moore DA, Veeriah S, Rosenthal R, Marafioti T, Kirkizlar E, Watkins TBK, McGranahan N, Ward S, Martinson L, Riley J, Fraioli F, Al Bakir M, Grönroos E, Zambrana F, Endozo R, Bi WL, Fennessy FM, Sponer N, Johnson D, Laycock J, Shafi S, Czyzewska-Khan J, Rowan A, Chambers T, Matthews N, Turajlic S, Hiley C, Lee SM, Forster MD, Ahmad T, Falzon M, Borg E, Lawrence D, Hayward M, Kolvekar S, Panagiotopoulos N, Janes SM, Thakrar R, Ahmed A, Blackhall F, Summers Y, Hafez D, Naik A, Ganguly A, Kareht S, Shah R, Joseph L, Marie Quinn A, Crosbie PA, Naidu B, Middleton G, Langman G, Trotter S, Nicolson M, Remmen H, Kerr K, Chetty M, Gomersall L, Fennell DA, Nakas A, Rathinam S, Anand G, Khan S, Russell P, Ezhil V, Ismail B, Irvin-Sellers M, Prakash V, Lester JF, Kornaszewska M, Attanoos R, Adams H, Davies H, Oukrif D, Akarca AU, Hartley JA, Lowe HL, Lock S, Iles N, Bell H, Ngai Y, Elgar G, Szallasi Z, Schwarz RF, Herrero J, Stewart A, Quezada SA, Peggs KS, Van Loo P, Dive C, Lin CJ, Rabinowitz M, Aerts HJWL, Hackshaw A, Shaw JA, Zimmermann BG, TRACERx consortium, PEACE consortium, Swanton C

Abstract

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.

MeSH 主题词
Biopsy/methods Carcinoma, Non-Small-Cell Lung/blood,genetics,pathology,surgery Cell Lineage/genetics Cell Tracking Clone Cells/metabolism,pathology DNA Mutational Analysis DNA, Neoplasm/blood,genetics Disease Progression Drug Resistance, Neoplasm/genetics Early Detection of Cancer/methods Evolution, Molecular Humans Limit of Detection Lung Neoplasms/blood,genetics,pathology,surgery Multiplex Polymerase Chain Reaction Neoplasm Metastasis/diagnosis,genetics,pathology Neoplasm Recurrence, Local/diagnosis,genetics,pathology Postoperative Care/methods Reproducibility of Results Tumor Burden
化学物质
DNA, Neoplasm
作者与单位
共 106 位作者,点击展开单位 / ORCID
Abbosh Christopher
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.
Birkbak Nicolai J
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. | Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Wilson Gareth A
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. | Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Jamal-Hanjani Mariam
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.
Constantin Tudor
Natera Inc., 201 Industrial Road, San Carlos, California 94070, USA.
Salari Raheleh
Natera Inc., 201 Industrial Road, San Carlos, California 94070, USA.
Le Quesne John
Cancer Studies, University of Leicester, Leicester LE2 7LX, UK.
Moore David A
Cancer Studies, University of Leicester, Leicester LE2 7LX, UK.
Veeriah Selvaraju
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.
Rosenthal Rachel
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.
Marafioti Teresa
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. | Department of Pathology, University College London Hospitals, 21 University Street, London WC1 6JJ, UK.
Kirkizlar Eser
Natera Inc., 201 Industrial Road, San Carlos, California 94070, USA.
Watkins Thomas B K
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. | Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
McGranahan Nicholas
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. | Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Ward Sophia
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. | Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. | Advanced Sequencing Facility, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Martinson Luke
Cancer Studies, University of Leicester, Leicester LE2 7LX, UK.
Riley Joan
Cancer Studies, University of Leicester, Leicester LE2 7LX, UK.
Fraioli Francesco
Department of Nuclear Medicine, University College London Hospitals, 235 Euston Road, Fitzrovia, London, NW1 2BU, UK.
Al Bakir Maise
Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Grönroos Eva
Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Zambrana Francisco
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.
Endozo Raymondo
Department of Nuclear Medicine, University College London Hospitals, 235 Euston Road, Fitzrovia, London, NW1 2BU, UK.
Bi Wenya Linda
Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. | Harvard Medical School, Boston, Massachusetts 02115, USA.
Fennessy Fiona M
Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. | Harvard Medical School, Boston, Massachusetts 02115, USA.
Sponer Nicole
Natera Inc., 201 Industrial Road, San Carlos, California 94070, USA.
Johnson Diana
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.
Laycock Joanne
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.
Shafi Seema
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.
Czyzewska-Khan Justyna
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.
Rowan Andrew
Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Chambers Tim
Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. | Advanced Sequencing Facility, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Matthews Nik
Advanced Sequencing Facility, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. | Tumour Profiling Unit Genomics Facility, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
Turajlic Samra
Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. | Renal and Skin Units, The Royal Marsden Hospital, London SW3 6JJ, UK.
Hiley Crispin
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. | Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Lee Siow Ming
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. | Department of Oncology, University College London Hospitals, 250 Euston Road, London NW1 2BU, UK.
Forster Martin D
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. | Department of Oncology, University College London Hospitals, 250 Euston Road, London NW1 2BU, UK.
Ahmad Tanya
Department of Oncology, University College London Hospitals, 250 Euston Road, London NW1 2BU, UK.
Falzon Mary
Department of Pathology, University College London Hospitals, 21 University Street, London WC1 6JJ, UK.
Borg Elaine
Department of Pathology, University College London Hospitals, 21 University Street, London WC1 6JJ, UK.
Lawrence David
Department of Cardiothoracic Surgery, University College London Hospitals, 235 Euston Road, Fitzrovia, London NW1 2BU, UK.
Hayward Martin
Department of Cardiothoracic Surgery, University College London Hospitals, 235 Euston Road, Fitzrovia, London NW1 2BU, UK.
Kolvekar Shyam
Department of Cardiothoracic Surgery, University College London Hospitals, 235 Euston Road, Fitzrovia, London NW1 2BU, UK.
Panagiotopoulos Nikolaos
Department of Cardiothoracic Surgery, University College London Hospitals, 235 Euston Road, Fitzrovia, London NW1 2BU, UK.
Janes Sam M
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. | Department of Respiratory Medicine, University College London Hospitals, 235 Euston Road, Fitzrovia, London NW1 2BU, UK. | Lungs for Living Research Centre, UCL Respiratory, Division of Medicine, Rayne Building, University College London, 5 University Street, London WC1E 6JF, UK.
Thakrar Ricky
Department of Respiratory Medicine, University College London Hospitals, 235 Euston Road, Fitzrovia, London NW1 2BU, UK.
Ahmed Asia
Department of Radiology, University College London Hospitals, 235 Euston Road, Fitzrovia, London NW1 2BU, UK.
Blackhall Fiona
Institute of Cancer Studies, University of Manchester, Oxford Road, Manchester M13 9PL, UK. | The Christie Hospital, Manchester M20 4BX, UK.
Summers Yvonne
The Christie Hospital, Manchester M20 4BX, UK.
Hafez Dina
Natera Inc., 201 Industrial Road, San Carlos, California 94070, USA.
Naik Ashwini
Natera Inc., 201 Industrial Road, San Carlos, California 94070, USA.
Ganguly Apratim
Natera Inc., 201 Industrial Road, San Carlos, California 94070, USA.
Kareht Stephanie
Natera Inc., 201 Industrial Road, San Carlos, California 94070, USA.
Shah Rajesh
Department of Cardiothoracic Surgery, University Hospital South Manchester, Manchester M23 9LT, UK.
Joseph Leena
Department of Pathology, University Hospital South Manchester, Manchester M23 9LT, UK.
Marie Quinn Anne
Department of Pathology, University Hospital South Manchester, Manchester M23 9LT, UK.
Crosbie Phil A
North West Lung Centre, University Hospital South Manchester, Manchester M23 9LT, UK.
Naidu Babu
Department of Thoracic Surgery, Birmingham Heartlands Hospital, Birmingham B9 5SS, UK. | Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK. University College London Hospitals NHS Foundation Trust, London, UK.
Middleton Gary
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
Langman Gerald
Department of Cellular Pathology, Birmingham Heartlands Hospital, Birmingham B9 5SS, UK.
Trotter Simon
Department of Cellular Pathology, Birmingham Heartlands Hospital, Birmingham B9 5SS, UK.
Nicolson Marianne
Department of Medical Oncology, Aberdeen University Medical School and Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, UK.
Remmen Hardy
Department of Cardiothoracic Surgery, Aberdeen University Medical School and Aberdeen Royal Infirmary, Aberdeen AB25 2ZD, UK.
Kerr Keith
Department of Pathology, Aberdeen University Medical School and Aberdeen Royal Infirmary, Aberdeen AB25 2ZD, UK.
Chetty Mahendran
Department of Respiratory Medicine, Aberdeen University Medical School and Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, UK.
Gomersall Lesley
Department of Radiology, Aberdeen University Medical School and Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, UK.
Fennell Dean A
Cancer Studies, University of Leicester, Leicester LE2 7LX, UK.
Nakas Apostolos
Department of Thoracic Surgery, Glenfield Hospital, Leicester LE3 9QP, UK.
Rathinam Sridhar
Department of Thoracic Surgery, Glenfield Hospital, Leicester LE3 9QP, UK.
Anand Girija
Department of Radiotherapy, North Middlesex University Hospital, London N18 1QX, UK.
Khan Sajid
Department of Respiratory Medicine, Royal Free Hospital, Pond Street, London NW3 2QG, UK. | Department of Respiratory Medicine, Barnet and Chase Farm Hospitals, Wellhouse Lane, Barnet EN5 3DJ, UK.
Russell Peter
Department of Respiratory Medicine, The Princess Alexandra Hospital, Hamstel Road, Harlow CM20 1QX, UK.
Ezhil Veni
Department of Clinical Oncology, St.Luke's Cancer Centre, Royal Surrey County Hospital, Guildford GU2 7XX, UK.
Ismail Babikir
Department of Pathology, Ashford and St. Peter's Hospital, Guildford Road, Chertsey, Surrey KT16 0PZ, UK.
Irvin-Sellers Melanie
Department of Respiratory Medicine, Ashford and St. Peter's Hospital, Guildford Road, Chertsey, Surrey KT16 0PZ, UK.
Prakash Vineet
Department of Radiology, Ashford and St. Peter's Hospital, Guildford Road, Chertsey, Surrey KT16 0PZ, UK.
Lester Jason F
Department of Clinical Oncology, Velindre Hospital, Cardiff CF14 2TL, UK.
Kornaszewska Malgorzata
Department of Cardiothoracic Surgery, University Hospital of Wales, Cardiff CF14 4XW, UK.
Attanoos Richard
Department of Cellular Pathology, University Hospital of Wales and Cardiff University, Heath Park, Cardiff, UK.
Adams Haydn
Department of Radiology, University Hospital Llandough, Cardiff CF64 2XX, UK.
Davies Helen
Department of Respiratory Medicine, University Hospital Llandough, Cardiff CF64 2XX, UK.
Oukrif Dahmane
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.
Akarca Ayse U
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.
Hartley John A
University College London Experimental Cancer Medicine Centre GCLP Facility, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, UK.
Lowe Helen L
University College London Experimental Cancer Medicine Centre GCLP Facility, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, UK.
Lock Sara
Department of Respiratory Medicine, The Whittington Hospital NHS Trust, London, N19 5NF, UK.
Iles Natasha
University College London, Cancer Research UK and UCL Cancer Trials Centre, London W1T 4TJ, UK.
Bell Harriet
University College London, Cancer Research UK and UCL Cancer Trials Centre, London W1T 4TJ, UK.
Ngai Yenting
University College London, Cancer Research UK and UCL Cancer Trials Centre, London W1T 4TJ, UK.
Elgar Greg
Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. | Advanced Sequencing Facility, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Szallasi Zoltan
Centre for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark. | Computational Health Informatics Program (CHIP), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA. | MTA-SE-NAP, Brain Metastasis Research Group, 2nd Department of Pathology, Semmelweis University, 1091 Budapest, Hungary.
Schwarz Roland F
Berlin Institute for Medical Systems Biology, Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
Herrero Javier
Bill Lyons Informatics Centre, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, UK.
Stewart Aengus
Department of Bioinformatics and Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Quezada Sergio A
Cancer Immunology Unit, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, UK.
Peggs Karl S
Cancer Immunology Unit, University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, UK. | Research Department of Haematology, University College Cancer Institute, London WC1E 6DD, UK.
Van Loo Peter
Cancer Genomics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. | Department of Human Genetics, University of Leuven, B-3000 Leuven, Belgium.
Dive Caroline
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. | Cancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
Lin C Jimmy
Natera Inc., 201 Industrial Road, San Carlos, California 94070, USA.
Rabinowitz Matthew
Natera Inc., 201 Industrial Road, San Carlos, California 94070, USA.
Aerts Hugo J W L
Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. | Harvard Medical School, Boston, Massachusetts 02115, USA. | Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215-5450, USA.
Hackshaw Allan
University College London, Cancer Research UK and UCL Cancer Trials Centre, London W1T 4TJ, UK.
Shaw Jacqui A
Cancer Studies, University of Leicester, Leicester LE2 7LX, UK.
Zimmermann Bernhard G
Natera Inc., 201 Industrial Road, San Carlos, California 94070, USA.
TRACERx consortium
PEACE consortium
Swanton Charles
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. | Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
Published
2017-00-26
页码
446-451
Language
English
Country/Region
England
NLM ID
0410462
基金资助
Medical Research Council · G108/596 · United Kingdom
NCATS NIH HHS · UL1 TR001863 · United States
Wellcome Trust · FC001169 · United Kingdom
Medical Research Council · MC_UP_1203/1 · United Kingdom
Wellcome Trust · FC001202 · United Kingdom
Wellcome Trust · United Kingdom
数据资源
ClinicalTrials.gov
NCT03004755
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