Chromosome instability was associated with an increased risk of recurrence and mortality among patients with early-stage non–small cell lung cancer (NSCLC), according to a study published in The New England Journal of Medicine.1

Previous studies of intratumor heterogeneity of NSCLC were small and retrospective. This study attempted to determine the effect of intratumor heterogeneity on clinical outcomes in a prospective setting.

The TRACERx prospective cohort study ( Identifier: NCT01888601) performed whole-exome sequencing on 100 tumors from patients with early-stage NSCLC resected prior to systemic therapy. The analysis included 327 tumor regions.

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There was substantial intratumor heterogeneity, primarily caused by dynamic chromosomal instability and genome doubling, for somatic copy-number alterations and mutations.

Clonal driver mutations occurred frequently in EGFR, MET, BRAF, and TP53, and over 75% of tumors developed driver mutations in PI3KCA and NF1 later in clonal evolution.

Chromosomal instability also resulted in parallel evolution of amplifications in CDK4, FOXA1, and BCL11A.

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An increased risk of recurrence or mortality was significantly associated with higher copy-number heterogeneity (hazard ratio, 4.9; P = .0004).

The authors wrote that this study “supports the potential value of chromosome instability as a prognostic predictor.”


  1. Jamal-Hanjani M, Wilson GA, McGranahan N, et al. Tracking the evolution of non–small-cell lung cancer. N Engl J Med. 2017 Apr 26. doi: 10.1056/NEJMoa161288 [Epub ahead of print]