Journal
SCIENCE
Volume 346, Issue 6206, Pages 256-259Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1256930
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Funding
- Cancer Prevention and Research Institute of Texas [R120501]
- University of Texas (UT) Systems Stars Award [PS100149]
- Welch Foundation Robert A. Welch Distinguished University Chair Award [G-0040]
- Department of Defense PROSPECT grant [W81XWH-07-1-0306]
- UT Lung Specialized Programs of Research Excellence grant [P50CA70907]
- MD Anderson Cancer Center Support grant [CA016672]
- NIH [CA-009666]
- MD Anderson Institutional Support for the Center for Translational and Public Health Genomics
- A. Lavoy Moore Endowment Fund
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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.
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