Journal Article

Lung Adenocarcinoma of Never Smokers and Smokers Harbor Differential Regions of Genetic Alteration and Exhibit Different Levels of Genomic Instability

Gazdar, Adi F., Zhang, Wei, English, John C., Chari, Raj, Fu, Rong, Feng, Ziding, Lam, Stephen, Thu, Kelsie L., MacAulay, Calum E., Vucic, Emily A., Lockwood, William W., Lam, Wan L., Wang, Pei

2012

Overview

Recent evidence suggests that the observed clinical distinctions between lung tumors in smokers and never smokers (NS) extend beyond specific gene mutations, such as EGFR, EML4-ALK, and KRAS, some of which have been translated into targeted therapies. However, the molecular alterations identified thus far cannot explain all of the clinical and biological disparities observed in lung tumors of NS and smokers. To this end, we performed an unbiased genome-wide, comparative study to identify novel genomic aberrations that differ between smokers and NS. High resolution whole genome DNA copy number profiling of 69 lung adenocarcinomas from smokers (n = 39) and NS (n = 30) revealed both global and regional disparities in the tumor genomes of these two groups. We found that NS lung tumors had a greater proportion of their genomes altered than those of smokers. Moreover, copy number gains on chromosomes 5q, 7p, and 16p occurred more frequently in NS. We validated our findings in two independently generated public datasets. Our findings provide a novel line of evidence distinguishing genetic differences between smoker and NS lung tumors, namely, that the extent of segmental genomic alterations is greater in NS tumors. Collectively, our findings provide evidence that these lung tumors are globally and genetically different, which implies they are likely driven by distinct molecular mechanisms.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aberration / Adenocarcinoma / Adenocarcinoma - genetics / Adenocarcinoma - pathology / Adenocarcinoma of Lung / Adult / Aged / Aged, 80 and over / Biology / chromosome 5 / Chromosomes / Comparative studies / Copy number / Deoxyribonucleic acid / DNA / DNA fingerprinting / Epidemiology / Epidermal growth factor receptors / ErbB Receptors - genetics / Female / Gene expression / Gene mutation / Genes, ras / Genetic aspects / Genomes / Genomic Instability / Genomics / Health sciences / Histology / Humans / K-Ras protein / Lung / Lung cancer / Lung Neoplasms - genetics / Lung Neoplasms - pathology / Lungs / Male / Medical research / Medicine / Middle Aged / Mitochondrial DNA / Molecular modelling / Mutation / Mutation Rate / Neoplasm Staging / Oncology / Ovarian cancer / Point mutation / Public health / Smokers / Smoking / Stability / Tumors