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Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Author

Listed:
  • Christopher Abbosh

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute)

  • Nicolai J. Birkbak

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute
    Translational Cancer Therapeutics Laboratory, The Francis Crick Institute)

  • Gareth A. Wilson

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute
    Translational Cancer Therapeutics Laboratory, The Francis Crick Institute)

  • Mariam Jamal-Hanjani

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute)

  • Tudor Constantin

    (Natera Inc.)

  • Raheleh Salari

    (Natera Inc.)

  • John Le Quesne

    (Cancer Studies, University of Leicester)

  • David A. Moore

    (Cancer Studies, University of Leicester)

  • Selvaraju Veeriah

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute)

  • Rachel Rosenthal

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute)

  • Teresa Marafioti

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute
    University College London Hospitals)

  • Eser Kirkizlar

    (Natera Inc.)

  • Thomas B. K. Watkins

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute
    Translational Cancer Therapeutics Laboratory, The Francis Crick Institute)

  • Nicholas McGranahan

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute
    Translational Cancer Therapeutics Laboratory, The Francis Crick Institute)

  • Sophia Ward

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute
    Translational Cancer Therapeutics Laboratory, The Francis Crick Institute
    Advanced Sequencing Facility, The Francis Crick Institute)

  • Luke Martinson

    (Cancer Studies, University of Leicester)

  • Joan Riley

    (Cancer Studies, University of Leicester)

  • Francesco Fraioli

    (University College London Hospitals)

  • Maise Al Bakir

    (Translational Cancer Therapeutics Laboratory, The Francis Crick Institute)

  • Eva Grönroos

    (Translational Cancer Therapeutics Laboratory, The Francis Crick Institute)

  • Francisco Zambrana

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute)

  • Raymondo Endozo

    (University College London Hospitals)

  • Wenya Linda Bi

    (Brigham and Women’s Hospital
    Harvard Medical School)

  • Fiona M. Fennessy

    (Brigham and Women’s Hospital
    Harvard Medical School)

  • Nicole Sponer

    (Natera Inc.)

  • Diana Johnson

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute)

  • Joanne Laycock

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute)

  • Seema Shafi

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute)

  • Justyna Czyzewska-Khan

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute)

  • Andrew Rowan

    (Translational Cancer Therapeutics Laboratory, The Francis Crick Institute)

  • Tim Chambers

    (Translational Cancer Therapeutics Laboratory, The Francis Crick Institute
    Advanced Sequencing Facility, The Francis Crick Institute)

  • Nik Matthews

    (Advanced Sequencing Facility, The Francis Crick Institute
    Tumour Profiling Unit Genomics Facility, The Institute of Cancer Research)

  • Samra Turajlic

    (Translational Cancer Therapeutics Laboratory, The Francis Crick Institute
    Renal and Skin Units, The Royal Marsden Hospital)

  • Crispin Hiley

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute
    Translational Cancer Therapeutics Laboratory, The Francis Crick Institute)

  • Siow Ming Lee

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute
    University College London Hospitals)

  • Martin D. Forster

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute
    University College London Hospitals)

  • Tanya Ahmad

    (University College London Hospitals)

  • Mary Falzon

    (University College London Hospitals)

  • Elaine Borg

    (University College London Hospitals)

  • David Lawrence

    (University College London Hospitals)

  • Martin Hayward

    (University College London Hospitals)

  • Shyam Kolvekar

    (University College London Hospitals)

  • Nikolaos Panagiotopoulos

    (University College London Hospitals)

  • Sam M. Janes

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute
    University College London Hospitals
    Lungs for Living Research Centre, UCL Respiratory, Rayne Building, University College London)

  • Ricky Thakrar

    (University College London Hospitals)

  • Asia Ahmed

    (University College London Hospitals)

  • Fiona Blackhall

    (Institute of Cancer Studies, University of Manchester
    The Christie Hospital)

  • Yvonne Summers

    (The Christie Hospital)

  • Dina Hafez

    (Natera Inc.)

  • Ashwini Naik

    (Natera Inc.)

  • Apratim Ganguly

    (Natera Inc.)

  • Stephanie Kareht

    (Natera Inc.)

  • Rajesh Shah

    (University Hospital South Manchester)

  • Leena Joseph

    (University Hospital South Manchester)

  • Anne Marie Quinn

    (University Hospital South Manchester)

  • Phil A. Crosbie

    (North West Lung Centre, University Hospital South Manchester)

  • Babu Naidu

    (Birmingham Heartlands Hospital
    Institute of Inflammation and Ageing, University of Birmingham)

  • Gary Middleton

    (Institute of Immunology and Immunotherapy, University of Birmingham)

  • Gerald Langman

    (Birmingham Heartlands Hospital)

  • Simon Trotter

    (Birmingham Heartlands Hospital)

  • Marianne Nicolson

    (Aberdeen University Medical School and Aberdeen Royal Infirmary)

  • Hardy Remmen

    (Aberdeen University Medical School and Aberdeen Royal Infirmary)

  • Keith Kerr

    (Aberdeen University Medical School and Aberdeen Royal Infirmary)

  • Mahendran Chetty

    (Aberdeen University Medical School and Aberdeen Royal Infirmary)

  • Lesley Gomersall

    (Aberdeen University Medical School and Aberdeen Royal Infirmary)

  • Dean A. Fennell

    (Cancer Studies, University of Leicester)

  • Apostolos Nakas

    (Glenfield Hospital)

  • Sridhar Rathinam

    (Glenfield Hospital)

  • Girija Anand

    (North Middlesex University Hospital)

  • Sajid Khan

    (Royal Free Hospital
    Barnet and Chase Farm Hospitals)

  • Peter Russell

    (The Princess Alexandra Hospital)

  • Veni Ezhil

    (St.Luke’s Cancer Centre, Royal Surrey County Hospital)

  • Babikir Ismail

    (Ashford and St. Peter’s Hospital)

  • Melanie Irvin-Sellers

    (Ashford and St. Peter’s Hospital)

  • Vineet Prakash

    (Ashford and St. Peter’s Hospital)

  • Jason F. Lester

    (Velindre Hospital)

  • Malgorzata Kornaszewska

    (University Hospital of Wales)

  • Richard Attanoos

    (University Hospital of Wales and Cardiff University)

  • Haydn Adams

    (University Hospital Llandough)

  • Helen Davies

    (University Hospital Llandough)

  • Dahmane Oukrif

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute)

  • Ayse U. Akarca

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute)

  • John A. Hartley

    (University College London Experimental Cancer Medicine Centre GCLP Facility, University College London Cancer Institute)

  • Helen L. Lowe

    (University College London Experimental Cancer Medicine Centre GCLP Facility, University College London Cancer Institute)

  • Sara Lock

    (The Whittington Hospital NHS Trust)

  • Natasha Iles

    (University College London, Cancer Research UK and UCL Cancer Trials Centre)

  • Harriet Bell

    (University College London, Cancer Research UK and UCL Cancer Trials Centre)

  • Yenting Ngai

    (University College London, Cancer Research UK and UCL Cancer Trials Centre)

  • Greg Elgar

    (Translational Cancer Therapeutics Laboratory, The Francis Crick Institute
    Advanced Sequencing Facility, The Francis Crick Institute)

  • Zoltan Szallasi

    (Centre for Biological Sequence Analysis, Technical University of Denmark
    Computational Health Informatics Program (CHIP), Boston Children’s Hospital, Harvard Medical School
    MTA-SE-NAP, Brain Metastasis Research Group, Semmelweis University)

  • Roland F. Schwarz

    (Berlin Institute for Medical Systems Biology, Max Delbrueck Center for Molecular Medicine)

  • Javier Herrero

    (Bill Lyons Informatics Centre, University College London Cancer Institute)

  • Aengus Stewart

    (The Francis Crick Institute)

  • Sergio A. Quezada

    (Cancer Immunology Unit, University College London Cancer Institute)

  • Karl S. Peggs

    (Cancer Immunology Unit, University College London Cancer Institute
    University College Cancer Institute)

  • Peter Van Loo

    (Cancer Genomics Laboratory, The Francis Crick Institute
    University of Leuven)

  • Caroline Dive

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute
    Cancer Research UK Manchester Institute, University of Manchester)

  • C. Jimmy Lin

    (Natera Inc.)

  • Matthew Rabinowitz

    (Natera Inc.)

  • Hugo J. W. L. Aerts

    (Brigham and Women’s Hospital
    Harvard Medical School
    Dana-Farber Cancer Institute)

  • Allan Hackshaw

    (University College London, Cancer Research UK and UCL Cancer Trials Centre)

  • Jacqui A. Shaw

    (Cancer Studies, University of Leicester)

  • Bernhard G. Zimmermann

    (Natera Inc.)

  • Charles Swanton

    (Cancer Research UK Lung Cancer Centre of Excellence London and Manchester, University College London Cancer Institute
    Translational Cancer Therapeutics Laboratory, The Francis Crick Institute)

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.

Suggested Citation

  • Christopher Abbosh & Nicolai J. Birkbak & Gareth A. Wilson & Mariam Jamal-Hanjani & Tudor Constantin & Raheleh Salari & John Le Quesne & David A. Moore & Selvaraju Veeriah & Rachel Rosenthal & Teresa , 2017. "Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution," Nature, Nature, vol. 545(7655), pages 446-451, May.
    • Handle: RePEc:nat:nature:v:545:y:2017:i:7655:d:10.1038_nature22364
    DOI: 10.1038/nature22364
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    Cited by:

    1. Bin Qiu & Wei Guo & Fan Zhang & Fang Lv & Ying Ji & Yue Peng & Xiaoxi Chen & Hua Bao & Yang Xu & Yang Shao & Fengwei Tan & Qi Xue & Shugeng Gao & Jie He, 2021. "Dynamic recurrence risk and adjuvant chemotherapy benefit prediction by ctDNA in resected NSCLC," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    2. Esther R. Berko & Gabriela M. Witek & Smita Matkar & Zaritza O. Petrova & Megan A. Wu & Courtney M. Smith & Alex Daniels & Joshua Kalna & Annie Kennedy & Ivan Gostuski & Colleen Casey & Kateryna Kryts, 2023. "Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. David Hsiehchen & Leslie Bucheit & Dong Yang & Muhammad Shaalan Beg & Mir Lim & Sunyoung S. Lee & Pashtoon Murtaza Kasi & Ahmed O. Kaseb & Hao Zhu, 2022. "Genetic features and therapeutic relevance of emergent circulating tumor DNA alterations in refractory non-colorectal gastrointestinal cancers," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    4. Nicolette M. Fonseca & Corinne Maurice-Dror & Cameron Herberts & Wilson Tu & William Fan & Andrew J. Murtha & Catarina Kollmannsberger & Edmond M. Kwan & Karan Parekh & Elena Schönlau & Cecily Q. Bern, 2024. "Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Dan Daniel Erdmann-Pham & Sanjit Singh Batra & Timothy K. Turkalo & James Durbin & Marco Blanchette & Iwei Yeh & Hunter Shain & Boris C. Bastian & Yun S. Song & Daniel S. Rokhsar & Dirk Hockemeyer, 2023. "Tracing cancer evolution and heterogeneity using Hi-C," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Mingyun Bae & Gyuhee Kim & Tae-Rim Lee & Jin Mo Ahn & Hyunwook Park & Sook Ryun Park & Ki Byung Song & Eunsung Jun & Dongryul Oh & Jeong-Won Lee & Young Sik Park & Ki-Won Song & Jeong-Sik Byeon & Bo H, 2023. "Integrative modeling of tumor genomes and epigenomes for enhanced cancer diagnosis by cell-free DNA," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Yi Zhou & Peng Ke & Xiaoyan Bao & Honghui Wu & Yiyi Xia & Zhentao Zhang & Haiqing Zhong & Qi Dai & Linjie Wu & Tiantian Wang & Mengting Lin & Yaosheng Li & Xinchi Jiang & Qiyao Yang & Yiying Lu & Xinc, 2022. "Peptide nano-blanket impedes fibroblasts activation and subsequent formation of pre-metastatic niche," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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