Jamal-Hanjani, M;
Wilson, GA;
McGranahan, N;
Birkbak, NJ;
Watkins, TBK;
Veeriah, S;
Shafi, S;
... Swanton, C; + view all
(2017)
Tracking the Evolution of Non-Small-Cell Lung Cancer.
New England Journal of Medicine
, 376
(22)
pp. 2109-2121.
10.1056/NEJMoa1616288.
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Abstract
Lung cancer is the leading cause of cancer-related death worldwide,1,2 with non–small-cell lung cancer (NSCLC) being the most common type. Large-scale sequencing studies have revealed the complex genomic landscape of NSCLC3-6 and genomic differences between lung adenocarcinomas and lung squamous-cell carcinomas.7 However, in-depth exploration of NSCLC intratumor heterogeneity (which provides the fuel for tumor evolution and drug resistance) and cancer genome evolution has been limited to small retrospective cohorts.8,9 Therefore, the clinical significance of intratumor heterogeneity and the potential for clonality of driver events to guide therapeutic strategies have not yet been defined. Tracking Non–Small-Cell Lung Cancer Evolution through Therapy (TRACERx)10 is a multicenter, prospective cohort study, which began recruitment in April 2014 with funding from Cancer Research UK. The target enrollment is 842 patients from whom samples will be obtained for high-depth, multiregion whole-exome sequencing of surgically resected NSCLC tumors in stages IA through IIIA. One primary objective of TRACERx is to investigate the hypothesis that intratumor heterogeneity — in terms of mutations (single or dinucleotide base substitutions or small insertions and deletions) or somatic copy-number alterations (reflecting gains or losses of chromosome segments) — is associated with clinical outcome. Here, we report on the first 100 patients who were prospectively recruited in the study.
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