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.

Original publication

DOI

10.1126/science.1256930

Type

Journal article

Journal

Science

Publication Date

10/10/2014

Volume

346

Pages

256 - 259

Keywords

Adenocarcinoma, DNA Mutational Analysis, Exome, Genes, Neoplasm, Genetic Heterogeneity, Humans, Lung Neoplasms, Mutation, Neoplasm Recurrence, Local