Tracking the Evolution of Non–Small-Cell Lung Cancer

Mariam Jamal‐Hanjani(Cancer Research UK), Gareth A. Wilson(Cancer Research UK), Nicholas McGranahan(Cancer Research UK), Nicolai J. Birkbak(Cancer Research UK), Thomas B.K. Watkins(Cancer Institute (WIA)), Selvaraju Veeriah(Cancer Research UK), Seema Shafi(Cancer Research UK), Diana Johnson(Cancer Research UK), Richard Mitter(CRUK Lung Cancer Centre of Excellence), Rachel Rosenthal(Cancer Research UK), Max Salm(CRUK Lung Cancer Centre of Excellence), Stuart Horswell(CRUK Lung Cancer Centre of Excellence), Mickael Escudero(CRUK Lung Cancer Centre of Excellence), Nik Matthews(CRUK Lung Cancer Centre of Excellence), Andrew Rowan(Cancer Institute (WIA)), Tim Chambers(Cancer Institute (WIA)), David A. Moore(University of Leicester), Samra Turajlic(Cancer Institute (WIA)), Hang Xu(Cancer Institute (WIA)), Siow Ming Lee(Cancer Research UK), Martin Förster(Cancer Research UK), Tanya Ahmad(CRUK Lung Cancer Centre of Excellence), Crispin T. Hiley(Cancer Institute (WIA)), Christopher Abbosh(Cancer Research UK), Mary Falzon(CRUK Lung Cancer Centre of Excellence), Elaine Borg(CRUK Lung Cancer Centre of Excellence), Teresa Marafioti(CRUK Lung Cancer Centre of Excellence), David Lawrence(CRUK Lung Cancer Centre of Excellence), Martin Hayward(CRUK Lung Cancer Centre of Excellence), Shyam Kolvekar(CRUK Lung Cancer Centre of Excellence), Nikolaos Panagiotopoulos(CRUK Lung Cancer Centre of Excellence), Sam M. Janes(Cancer Research UK), Ricky M. Thakrar(CRUK Lung Cancer Centre of Excellence), Asia Ahmed(CRUK Lung Cancer Centre of Excellence), Fiona Blackhall(University of Manchester), Yvonne Summers(The Christie Hospital), Rajesh Shah(CRUK Lung Cancer Centre of Excellence), Leena Dennis Joseph(CRUK Lung Cancer Centre of Excellence), Anne Marie Quinn(CRUK Lung Cancer Centre of Excellence), Philip Crosbie(CRUK Lung Cancer Centre of Excellence), Babu Naidu(CRUK Lung Cancer Centre of Excellence), Gary Middleton(Institute of Immunology), Gerald Langman(CRUK Lung Cancer Centre of Excellence), Simon Trotter(CRUK Lung Cancer Centre of Excellence), M. Nicolson(Birmingham General Hospital), Hardy Remmen(CRUK Lung Cancer Centre of Excellence), Keith M. Kerr(CRUK Lung Cancer Centre of Excellence), Mahendran Chetty(CRUK Lung Cancer Centre of Excellence), Lesley Gomersall(CRUK Lung Cancer Centre of Excellence), Dean A. Fennell(University of Leicester), Apostolos Nakas(Glenfield Hospital), Sridhar Rathinam(Glenfield Hospital), Girija Anand(CRUK Lung Cancer Centre of Excellence), Sajid Khan(Aberdeen Royal Infirmary), Peter Russell(CRUK Lung Cancer Centre of Excellence), Veni Ezhil(CRUK Lung Cancer Centre of Excellence), Babikir Ismail(CRUK Lung Cancer Centre of Excellence), Melanie Irvin-Sellers(CRUK Lung Cancer Centre of Excellence), Vineet Prakash(CRUK Lung Cancer Centre of Excellence), J.F. Lester(St Peter's Hospital), Malgorzata Kornaszewska(CRUK Lung Cancer Centre of Excellence), Richard Attanoos(University Hospital of Wales), Haydn Adams(CRUK Lung Cancer Centre of Excellence), Helen Davies(Respiratory Clinical Trials), Stefan C. Dentro(Wellcome Sanger Institute), Philippe Tanière(Heartlands Hospital), Brendan O’Sullivan(Heartlands Hospital), Helen L. Lowe(CRUK Lung Cancer Centre of Excellence), John A. Hartley(CRUK Lung Cancer Centre of Excellence), Natasha Iles(Cancer Research UK), Harriet Bell(Cancer Research UK), Yenting Ngai(Cancer Research UK), Jacqui Shaw(University of Leicester), Javier Herrero(CRUK Lung Cancer Centre of Excellence), Zoltán Szállási(Semmelweis University), Roland F. Schwarz(Max Delbrück Center), Aengus Stewart(CRUK Lung Cancer Centre of Excellence), Sergio A. Quezada(CRUK Lung Cancer Centre of Excellence), John Le Quesne(University of Leicester), Peter Van Loo(Cancer Genomics Centre), Caroline Dive(Cancer Research UK), Allan Hackshaw(Cancer Research UK), Charles Swanton(Cancer Research UK)
New England Journal of Medicine
April 26, 2017
10.1056/nejmoa1616288
Cited by 2,418Open Access
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Abstract

BACKGROUND: Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. METHODS: In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy. We sequenced and analyzed 327 tumor regions to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between intratumor heterogeneity and recurrence-free survival. RESULTS: ), which remained significant in multivariate analysis. CONCLUSIONS: Intratumor heterogeneity mediated through chromosome instability was associated with an increased risk of recurrence or death, a finding that supports the potential value of chromosome instability as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .).

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