Conserved recurrent gene mutations correlate with pathway deregulation and clinical outcomes of lung adenocarcinoma in never-smokers. BMC Med Genomics 2014 Jun 04;7:32
Date
06/05/2014Pubmed ID
24894543Pubmed Central ID
PMC4060138DOI
10.1186/1755-8794-7-32Scopus ID
2-s2.0-84902810152 (requires institutional sign-in at Scopus site) 53 CitationsAbstract
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.
Author List
Sun Z, Wang L, Eckloff BW, Deng B, Wang Y, Wampfler JA, Jang J, Wieben ED, Jen J, You M, Yang PMESH terms used to index this publication - Major topics in bold
AdenocarcinomaConserved Sequence
DNA Mutational Analysis
DNA, Neoplasm
Exome
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Kaplan-Meier Estimate
Lung Neoplasms
Male
Middle Aged
Mutation
Polymorphism, Single Nucleotide
RNA, Messenger
Reproducibility of Results
Signal Transduction
Smoking
Treatment Outcome
