Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing
- PMID: 25301631
- PMCID: PMC4354858
- DOI: 10.1126/science.1256930
Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing
Abstract
Cancers are composed of populations of cells with distinct molecular and phenotypic features, a phenomenon termed intratumor heterogeneity (ITH). ITH in lung cancers has not been well studied. We applied multiregion whole-exome sequencing (WES) on 11 localized lung adenocarcinomas. All tumors showed clear evidence of ITH. On average, 76% of all mutations and 20 out of 21 known cancer gene mutations were identified in all regions of individual tumors, which suggested that single-region sequencing may be adequate to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. With a median follow-up of 21 months after surgery, three patients have relapsed, and all three patients had significantly larger fractions of subclonal mutations in their primary tumors than patients without relapse. These data indicate that a larger subclonal mutation fraction may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas.
Copyright © 2014, American Association for the Advancement of Science.
Figures
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Comment in
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Cancer. Attack of the clones.Science. 2014 Oct 10;346(6206):169-70. doi: 10.1126/science.1259926. Science. 2014. PMID: 25301605 No abstract available.
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Lung cancer: Heterogeneity in space and time.Nat Rev Clin Oncol. 2014 Dec;11(12):684. doi: 10.1038/nrclinonc.2014.186. Epub 2014 Oct 28. Nat Rev Clin Oncol. 2014. PMID: 25348786 No abstract available.
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