Phylogenetic ctDNA analysis depicts early-stage lung cancer evolutionMore about Open Access at the Crick
Authors listChristopher Abbosh Nicolai Birkbak Gareth Wilson Mariam Jamal-Hanjani Tudor Constantin Raheleh Salari John Le Quesne David A Moore Selvaraju Veeriah Rachel Rosenthal Teresa Marafioti Eser Kirkizlar Tom Watkins Nicholas McGranahan Sophie Ward Luke Martinson Joan Riley Francesco Fraioli Maise Al Bakir Eva Gronroos 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 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 Peter Van Loo Caroline Dive C Jimmy Lin Matthew Rabinowitz Hugo JWL Aerts Allan Hackshaw Jacqui A Shaw Bernhard G Zimmermann The TRACERx Consortium The PEACE Consortium Charles Swanton
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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.
Issue number 7655