Smoking-related genomic signatures in non-small cell lung cancer

Pierre P. Massion, Yong Zou, Heidi Chen, Aixiang Jiang, Peter Coulson, Christopher I. Amos, Xifeng Wu, Ignacio Wistuba, Qingyi Wei, Yu Shyr, Margaret R. Spitz

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Rationale: Tobacco smoking is responsible for 85% of all lung cancers. To further our understanding of the molecular pathogenesis of lung cancer, we determined whether smoking history leads to the emergence of specific genomic alterations found in non-small cell lung cancer (NSCLC). Objectives: To identify gene copy number alterations in NSCLCs associated with smoking history or DNA repair capacity. Methods: Seventy-five NSCLCs were selected for this study from patients with current, none, or past smoking history, including pack year information. Tissue sections were microdissected, and DNA was extracted, purified, and labeled by random priming before hybridization onto bacterial artificial chromosome (BAC) arrays. Normalized ratios were correlated with smoking history and DNA repair capacity was measured by an in vitro lymphocyte assay in the same patients. Measurements and Main Results: We identified smoking-related genomic signatures in NSCLCs that could be predicted with an overall 74% accuracy. Lung tumors arising from current-smokers had the greatest number of copy number alterations. The genomic regions most significantly associated with smoking were located within 60 regions and were functionally associated with genes controlling the M phase of the cell cycle, the segregation of chromosomes, and the methylation of DNA. Verification of the data is provided from data in the public domain and by quantitative real-time polymerase chain reaction. The associations between genomic abnormalities and DNA repair capacity did not reach statistical significance. Conclusions: These findings indicate that smoking history leaves a specific genomic signature in the DNA of lung tumors and suggest that these alterations may reflect new molecular pathways to cancer development.

Original languageEnglish
Pages (from-to)1164-1172
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume178
Issue number11
DOIs
Publication statusPublished - 2008 Dec 1

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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  • Cite this

    Massion, P. P., Zou, Y., Chen, H., Jiang, A., Coulson, P., Amos, C. I., Wu, X., Wistuba, I., Wei, Q., Shyr, Y., & Spitz, M. R. (2008). Smoking-related genomic signatures in non-small cell lung cancer. American Journal of Respiratory and Critical Care Medicine, 178(11), 1164-1172. https://doi.org/10.1164/rccm.200801-142OC