Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

Christopher Abbosh, Nicolai Juul 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 GrönroosFrancisco Zambrana, Raymondo Endozo, Wenya Linda Bi, Fiona M. Fennessy, Nicole Sponer, Diana H. Johnson, Joanne Laycock, Seema Shafi, Justyna Czyzewska-Khan, Andrew Rowan, Tim Chambers, Nik Matthews, Samra Turajlic, Crispin T. 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, Ashwini Naik, Apratim Ganguly, Stephanie Kareht, Rajesh Shah, Leena Joseph, Anne Marie Quinn, Phil A. Crosbie, Babu Naidu, Gary Middleton, Gerald Langman, Simon Trotter, Marianne Nicolson, Hardy Remmen, Keith Kerr, Mahendran Chetty, Lesley Gomersall, Dean A. Fennell, Apostolos Nakas, Sridhar Rathinam, Girija Anand, Sajid Khan, Peter Russell, Veni Ezhil, Babikir Ismail, Melanie Irvin-Sellers, Vineet Prakash, Jason F. Lester, Malgorzata Kornaszewska, Richard Attanoos, Haydn Adams, Helen Davies, Dahmane Oukrif, Ayse U. Akarca, John A. Hartley, Helen L Lowe, Sara Lock, Natasha Iles, Harriet Bell, Yenting Ngai, Greg Elgar, Zoltan Imre Szallasi, Roland F. Schwarz, Javier Herrero, Aengus Stewart, Sergio A. Quezada, Peter Van Loo, Caroline Dive, C. Jimmy Lin, Matthew Rabinowitz, Hugo J.W.L. Aerts, Allan Hackshaw, Jacqui A. Shaw, Bernhard G. Zimmermann, Charles Swanton

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastases, providing a new approach for ctDNA driven therapeutic studies.
    Original languageEnglish
    JournalNature
    Volume545
    Pages (from-to)446-451
    Number of pages21
    ISSN0028-0836
    DOIs
    Publication statusPublished - 2017

    Cite this

    Abbosh, C., Birkbak, N. J., Wilson, G. A., Jamal-Hanjani, M., Constantin, T., Salari, R., Quesne, J. L., Moore, D. A., Veeriah, S., Rosenthal, R., Marafioti, T., Kirkizlar, E., Watkins, T. B. K., McGranahan, N., Ward, S., Martinson, L., Riley, J., Fraioli, F., Bakir, M. A., ... Swanton, C. (2017). Phylogenetic ctDNA analysis depicts early stage lung cancer evolution. Nature, 545, 446-451. https://doi.org/10.1038/nature22364