Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing

J Zhang, J Fujimoto, J Zhang, DC Wedge, X Song…�- Science, 2014 - science.org
J Zhang, J Fujimoto, J Zhang, DC Wedge, X Song, J Zhang, S Seth, CW Chow, Y Cao…
Science, 2014science.org
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�…
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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