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Epigenomic analysis of lung adenocarcinoma reveals novel DNA methylation patterns associated with smoking
The importance of epigenetic regulation has been increasingly recognized in the development of cancer. In this study, we investigated the impact of smoking, a major risk factor of lung cancer, on DNA methylation by comparing the genome-wide DNA methylation patterns between lung adenocarcinoma sample...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818101/ https://www.ncbi.nlm.nih.gov/pubmed/24204162 http://dx.doi.org/10.2147/OTT.S51041 |
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author | Tan, Qiang Wang, Guan Huang, Jia Ding, Zhengping Luo, Qingquan Mok, Tony Tao, Qian Lu, Shun |
author_facet | Tan, Qiang Wang, Guan Huang, Jia Ding, Zhengping Luo, Qingquan Mok, Tony Tao, Qian Lu, Shun |
author_sort | Tan, Qiang |
collection | PubMed |
description | The importance of epigenetic regulation has been increasingly recognized in the development of cancer. In this study, we investigated the impact of smoking, a major risk factor of lung cancer, on DNA methylation by comparing the genome-wide DNA methylation patterns between lung adenocarcinoma samples from six smokers and six nonsmokers. We identified that smoking-induced DNA methylations were enriched in the calcium signaling and neuroactive ligand receptor signaling pathways, which are closely related to smoking-induced lung cancers. Interestingly, we discovered that two genes in the mitogen-activated protein kinase signaling pathway (RPS6KA3 and ARAF) were hypomethylated in smokers but not in nonsmokers. In addition, we found that the smoking-induced lung cancer-specific DNA methylations were mostly enriched in nuclear activities, including regulation of gene expression and chromatin remodeling. Moreover, the smoking-induced hypermethylation could only be seen in lung adenocarcinoma tissue but not in adjacent normal lung tissue. We also used differentially methylated DNA loci to construct a diagnostic model to distinguish smoking-associated lung cancer from nonsmoking lung cancer with a sensitivity of 88.9% and specificity of 83.2%. Our results provided novel evidence to support that smoking can cause dramatic changes in the DNA methylation landscape of lung cancer, suggesting that epigenetic regulation of specific oncogenic signaling pathways plays an important role in the development of lung cancer. |
format | Online Article Text |
id | pubmed-3818101 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-38181012013-11-07 Epigenomic analysis of lung adenocarcinoma reveals novel DNA methylation patterns associated with smoking Tan, Qiang Wang, Guan Huang, Jia Ding, Zhengping Luo, Qingquan Mok, Tony Tao, Qian Lu, Shun Onco Targets Ther Original Research The importance of epigenetic regulation has been increasingly recognized in the development of cancer. In this study, we investigated the impact of smoking, a major risk factor of lung cancer, on DNA methylation by comparing the genome-wide DNA methylation patterns between lung adenocarcinoma samples from six smokers and six nonsmokers. We identified that smoking-induced DNA methylations were enriched in the calcium signaling and neuroactive ligand receptor signaling pathways, which are closely related to smoking-induced lung cancers. Interestingly, we discovered that two genes in the mitogen-activated protein kinase signaling pathway (RPS6KA3 and ARAF) were hypomethylated in smokers but not in nonsmokers. In addition, we found that the smoking-induced lung cancer-specific DNA methylations were mostly enriched in nuclear activities, including regulation of gene expression and chromatin remodeling. Moreover, the smoking-induced hypermethylation could only be seen in lung adenocarcinoma tissue but not in adjacent normal lung tissue. We also used differentially methylated DNA loci to construct a diagnostic model to distinguish smoking-associated lung cancer from nonsmoking lung cancer with a sensitivity of 88.9% and specificity of 83.2%. Our results provided novel evidence to support that smoking can cause dramatic changes in the DNA methylation landscape of lung cancer, suggesting that epigenetic regulation of specific oncogenic signaling pathways plays an important role in the development of lung cancer. Dove Medical Press 2013-10-21 /pmc/articles/PMC3818101/ /pubmed/24204162 http://dx.doi.org/10.2147/OTT.S51041 Text en © 2013 Tan et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Tan, Qiang Wang, Guan Huang, Jia Ding, Zhengping Luo, Qingquan Mok, Tony Tao, Qian Lu, Shun Epigenomic analysis of lung adenocarcinoma reveals novel DNA methylation patterns associated with smoking |
title | Epigenomic analysis of lung adenocarcinoma reveals novel DNA methylation patterns associated with smoking |
title_full | Epigenomic analysis of lung adenocarcinoma reveals novel DNA methylation patterns associated with smoking |
title_fullStr | Epigenomic analysis of lung adenocarcinoma reveals novel DNA methylation patterns associated with smoking |
title_full_unstemmed | Epigenomic analysis of lung adenocarcinoma reveals novel DNA methylation patterns associated with smoking |
title_short | Epigenomic analysis of lung adenocarcinoma reveals novel DNA methylation patterns associated with smoking |
title_sort | epigenomic analysis of lung adenocarcinoma reveals novel dna methylation patterns associated with smoking |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818101/ https://www.ncbi.nlm.nih.gov/pubmed/24204162 http://dx.doi.org/10.2147/OTT.S51041 |
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