title: Conserved recurrent gene mutations correlate with pathway deregulation and clinical outcomes of lung adenocarcinoma in never-smokers.
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.
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. sun.zhifu@mayo.edu.
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Sun
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Eckloff
authors.forename: Bo
authors.initials: B
authors.lastname: Deng
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Jason A
authors.initials: JA
authors.lastname: Wampfler
authors.forename: JinSung
authors.initials: J
authors.lastname: Jang
authors.forename: Eric D
authors.initials: ED
authors.lastname: Wieben
authors.forename: Jin
authors.initials: J
authors.lastname: Jen
authors.forename: Ming
authors.initials: M
authors.lastname: You
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D017124:Conserved Sequence / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D059472:Exome / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm; D012333:RNA, Messenger