Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-05

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, 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 Szallasi, Roland F. Schwarz, Javier Herrero, Aengus Stewart, Sergio A. Quezada, Karl S. Peggs, Peter Van Loo, Caroline Dive, C. Jimmy Lin, Matthew Rabinowitz, Hugo J. W. L. Aerts, Allan Hackshaw, Jacqui A. Shaw, Bernhard G. Zimmermann, The TRACERx consortium, Charles Swanton, Leticia Bosshard-Carter, Gerald Goh, Pat Gorman, Nirupa Murugaesu, Robert E. Hynds, Stuart Horswell, Richard Mitter, Mickael Escudero, Hang Xu, Jacki Goldman, Richard Kevin Stone, Tamara Denner, Jennifer Biggs, Marta Costa, Sharmin Begum, Ben Phillimore, Emma Nye, Sofia Graca, Kroopa Joshi, Andrew Furness, Assma Ben Aissa, Yien Ning Sophia Wong, Andy Georgiou, Celia Simeon, Gemma Hector, Amy Smith, Marie Aranda, Marco Novelli, Dionysis Papadatos-Pastos, Dawn Carnell, Ruheena Mendes, Jeremy George, Neal Navani, Magali Taylor, Junaid Choudhary, Raffaele Califano, Paul Taylor, Piotr Krysiak, Kendadai Rammohan, Eustace Fontaine, Richard Booton, Matthew Evison, Stuart Moss, Faiza Idries, Paul Bishop, Anshuman Chaturvedi, Helen Doran, Angela Leek, Phil Harrison, Katrina Moore, Rachael Waddington, Juliette Novasio, Jane Rogan, Elaine Smith, Jonathan Tugwood, Ged Brady, Dominic G. Rothwell, Francesca Chemi, Jackie Pierce, Sakshi Gulati, Mary Bellamy, Hollie Bancroft, Amy Kerr, Salma Kadiri, Joanne Webb, Madava Djearaman, Anne Thomas, Harriet Walter, William Monteiro, Hilary Marshall, Louise Nelson, Jonathan Bennett, Lindsay Primrose, Anita Amadi, Shirley Palmer, Joy Miller, Keith Buchan, Alison Edwards, Fiona Morgan, Azmina Verjee, Mairead MacKenzie, Maggie Wilcox, Sean Smith, Nicole Gower, Christian Ottensmeier, Serena Chee, Benjamin Johnson, Aiman Alzetani, Emily Shaw, Eric Lim, Paulo De Sousa, Monica Tavares Barbosa, Alex Bowman, Simon Jordan, Alexandra Rice, Hilgardt Raubenheimer, Chiara Proli, Maria Elena Cufari, John Carlo Ronquillo, Angela Kwayie, Harshil Bhayani, Morag Hamilton, Yusura Bakar, Natalie Mensah, Lyn Ambrose, Anand Devaraj, Silviu Buderi, Jonathan Finch, Leire Azcarate, Hema Chavan, Sophie Green, Hillaria Mashinga, Andrew G. Nicholson, Kelvin Lau, Michael Sheaff, Peter Schmid, John Conibear, Teresa Light, Tracey Horey, Sarah Danson, Jonathan Bury, John Edwards, Jennifer Hill, Sue Matthews, Yota Kitsanta, Kim Suvarna, Patricia Fisher, Allah Dino Keerio, Michael Shackcloth, John Gosney, Pieter Postmus, Sarah Feeney, Julius Asante-Siaw, Stefan Dentro, Christophe Dessimoz, The PEACE consortium

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. More... »

PAGES

446

Journal

TITLE

Nature

ISSUE

7655

VOLUME

545

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature22364

DOI

http://dx.doi.org/10.1038/nature22364

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1085068314

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28445469


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55 schema:description 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.
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