Dataset Information

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.

SUBMITTER: Sun Z

PROVIDER: S-EPMC4060138 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Sun Zhifu Z Wang Liang L Eckloff Bruce W BW Deng Bo B Wang Yi Y Wampfler Jason A JA Jang JinSung J Wieben Eric D ED Jen Jin J You Ming M Yang Ping P

BMC medical genomics 20140604

<h4>Background</h4>Novel and targetable mutations are needed for improved understanding and treatment of lung cancer in never-smokers.<h4>Methods</h4>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.<h4>Results</h4>Although somatic mutations in DNA or mRNA ranged from hundreds to thousands in each tumor, the o ...[more]

PMID: 24894543

Similar Datasets

Project description:IntroductionHistorically, high rates of actionable driver mutations have been reported in never-smokers with lung adenocarcinoma (ADC). In the era of modern, comprehensive cancer mutation sequencing, this relationship necessitates a more detailed analysis.MethodsAll Mount Sinai patients between January 1, 2015, and June 1, 2020, with a diagnosis of ADC of any stage with known smoking status who received genomic testing were included. Most patients were analyzed using the Sema4 hotspot panel or the Oncomine Comprehensive Assay version 3 next-generation sequencing (NGS) panel conducted at Sema4. Patients were considered fully genotyped if they were comprehensively analyzed for alterations in EGFR, KRAS, MET, ALK, RET, ROS1, BRAF, NTRK1-3, and ERBB2, otherwise they were considered partially genotyped.ResultsTwo hundred and thirty-six never-smokers and 671 smokers met the above criteria. Of the never-smokers, 201 (85%) had a driver mutation with 167 (71%) considered actionable (ie, those with US Food and Drug Administration-approved agents). Among smokers, 439 (65%) had an identified driver mutation with 258 (38%) actionable (P < .0001). When comprehensively sequenced, 95% (70/74) of never-smokers had a driver mutation with 78% (58/74) actionable; whereas, for smokers, 75% (135/180) had a driver with only 47% (74/180) actionable (P < .0001). Within mutations groups, EGFR G719X and KRAS G12Cs were more common to smokers. For stage IV patients harboring EGFR-mutant tumors treated with EGFR-directed therapies, never-smokers had significantly improved OS compared to smokers (hazard ratio = 2.71; P = .025). In multivariable analysis, Asian ancestry and female sex remained significant predictors of (1) OS in stage IV patients and (2) likelihood of harboring a receptor of fusion-based driver.ConclusionComprehensive NGS revealed driver alterations in 95% of never-smokers, with the majority having an associated therapy available. All efforts should be exhausted to identify or rule out the presence of an actionable driver mutation in all metastatic lung ADC.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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