Conserved recurrent gene mutations correlate with pathway deregulation and clinical outcomes of lung adenocarcinoma in never-smokers

Zhifu Sun, Liang Wang, Bruce W. Eckloff, Bo Deng, Yi Wang, Jason A. Wampfler, Jinsung Jang, Eric D. Wieben, Jin Jen, Ming You, Ping Yang

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Novel and targetable mutations are needed for improved understanding and treatment of lung cancer in never-smokers. Methods. Twenty-seven lung adenocarcinomas from never-smokers were sequenced by both exome and mRNA-seq with respective normal tissues. Somatic mutations were detected and compared with pathway deregulation, tumor phenotypes and clinical outcomes. Results: Although somatic mutations in DNA or mRNA ranged from hundreds to thousands in each tumor, the overlap mutations between the two were only a few to a couple of hundreds. The number of somatic mutations from either DNA or mRNA was not significantly associated with clinical variables; however, the number of overlap mutations was associated with cancer subtype. These overlap mutants were preferentially expressed in mRNA with consistently higher allele frequency in mRNA than in DNA. Ten genes (EGFR, TP53, KRAS, RPS6KB2, ATXN2, DHX9, PTPN13, SP1, SPTAN1 and MYOF) had recurrent mutations and these mutations were highly correlated with pathway deregulation and patient survival. Conclusions: The recurrent mutations present in both DNA and RNA are likely the driver for tumor biology, pathway deregulation and clinical outcomes. The information may be used for patient stratification and therapeutic target development.

Original languageEnglish (US)
Article number32
JournalBMC Medical Genomics
Volume7
Issue number1
DOIs
StatePublished - Jun 4 2014
Externally publishedYes

Keywords

  • Lung adenocarcinoma of never smoker
  • Pathway deregulation
  • Patient survival
  • Somatic mutations

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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