Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution

Research output: Contribution to journalArticle

Authors

  • 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 Marafioti
  • Eser Kirkizlar
  • Thomas B K Watkins
  • Nicholas McGranahan
  • Sophia Ward
  • Luke Martinson
  • Joan Riley
  • Francesco Fraioli
  • Maise Al Bakir
  • Eva Grönroos
  • Francisco Zambrana
  • Raymondo Endozo
  • Wenya Linda Bi
  • Fiona M Fennessy
  • Nicole Sponer
  • Diana Johnson
  • Joanne Laycock
  • Seema Shafi
  • Justyna Czyzewska-Khan
  • Andrew Rowan
  • Tim Chambers
  • Nik Matthews
  • Samra Turajlic
  • Crispin Hiley
  • Siow Ming Lee
  • Martin D Forster
  • Tanya Ahmad
  • Mary Falzon
  • Elaine Borg
  • David Lawrence
  • Martin Hayward
  • Shyam Kolvekar
  • Nikolaos Panagiotopoulos
  • Sam M Janes
  • Ricky Thakrar
  • Asia Ahmed
  • Fiona Blackhall
  • Yvonne Summers
  • Dina Hafez
  • Gary Middleton
  • TRACERx consortium

Colleges, School and Institutes

External organisations

  • 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.

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.

Details

Original languageEnglish
Pages (from-to)446-451
Number of pages6
JournalNature
Volume545
Issue number7655
Early online date26 Apr 2017
Publication statusPublished - 25 May 2017

Keywords

  • Non-small-cell lung cancer, Tumour heterogeneity, Metastasis , Diagnostic markers, Predictive markers