Cargando…
Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression
Lung cancer is the leading cause of cancer death worldwide, and adenocarcinoma is its most common histological subtype. Clinical and molecular evidence indicates that lung adenocarcinoma is a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DNA me...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396362/ https://www.ncbi.nlm.nih.gov/pubmed/22613842 http://dx.doi.org/10.1101/gr.132662.111 |
_version_ | 1782238107276410880 |
---|---|
author | Selamat, Suhaida A. Chung, Brian S. Girard, Luc Zhang, Wei Zhang, Ying Campan, Mihaela Siegmund, Kimberly D. Koss, Michael N. Hagen, Jeffrey A. Lam, Wan L. Lam, Stephen Gazdar, Adi F. Laird-Offringa, Ite A. |
author_facet | Selamat, Suhaida A. Chung, Brian S. Girard, Luc Zhang, Wei Zhang, Ying Campan, Mihaela Siegmund, Kimberly D. Koss, Michael N. Hagen, Jeffrey A. Lam, Wan L. Lam, Stephen Gazdar, Adi F. Laird-Offringa, Ite A. |
author_sort | Selamat, Suhaida A. |
collection | PubMed |
description | Lung cancer is the leading cause of cancer death worldwide, and adenocarcinoma is its most common histological subtype. Clinical and molecular evidence indicates that lung adenocarcinoma is a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DNA methylation profiling using the Illumina Infinium HumanMethylation27 platform on 59 matched lung adenocarcinoma/non-tumor lung pairs, with genome-scale verification on an independent set of tissues. We identified 766 genes showing altered DNA methylation between tumors and non-tumor lung. By integrating DNA methylation and mRNA expression data, we identified 164 hypermethylated genes showing concurrent down-regulation, and 57 hypomethylated genes showing increased expression. Integrated pathways analysis indicates that these genes are involved in cell differentiation, epithelial to mesenchymal transition, RAS and WNT signaling pathways, and cell cycle regulation, among others. Comparison of DNA methylation profiles between lung adenocarcinomas of current and never-smokers showed modest differences, identifying only LGALS4 as significantly hypermethylated and down-regulated in smokers. LGALS4, encoding a galactoside-binding protein involved in cell–cell and cell–matrix interactions, was recently shown to be a tumor suppressor in colorectal cancer. Unsupervised analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation and was significantly associated with KRAS mutation and to a lesser extent, with smoking. Our analysis lays the groundwork for further molecular studies of lung adenocarcinoma by identifying novel epigenetically deregulated genes potentially involved in lung adenocarcinoma development/progression, and by describing an epigenetic subgroup of lung adenocarcinoma associated with characteristic molecular alterations. |
format | Online Article Text |
id | pubmed-3396362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-33963622013-01-01 Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression Selamat, Suhaida A. Chung, Brian S. Girard, Luc Zhang, Wei Zhang, Ying Campan, Mihaela Siegmund, Kimberly D. Koss, Michael N. Hagen, Jeffrey A. Lam, Wan L. Lam, Stephen Gazdar, Adi F. Laird-Offringa, Ite A. Genome Res Research Lung cancer is the leading cause of cancer death worldwide, and adenocarcinoma is its most common histological subtype. Clinical and molecular evidence indicates that lung adenocarcinoma is a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DNA methylation profiling using the Illumina Infinium HumanMethylation27 platform on 59 matched lung adenocarcinoma/non-tumor lung pairs, with genome-scale verification on an independent set of tissues. We identified 766 genes showing altered DNA methylation between tumors and non-tumor lung. By integrating DNA methylation and mRNA expression data, we identified 164 hypermethylated genes showing concurrent down-regulation, and 57 hypomethylated genes showing increased expression. Integrated pathways analysis indicates that these genes are involved in cell differentiation, epithelial to mesenchymal transition, RAS and WNT signaling pathways, and cell cycle regulation, among others. Comparison of DNA methylation profiles between lung adenocarcinomas of current and never-smokers showed modest differences, identifying only LGALS4 as significantly hypermethylated and down-regulated in smokers. LGALS4, encoding a galactoside-binding protein involved in cell–cell and cell–matrix interactions, was recently shown to be a tumor suppressor in colorectal cancer. Unsupervised analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation and was significantly associated with KRAS mutation and to a lesser extent, with smoking. Our analysis lays the groundwork for further molecular studies of lung adenocarcinoma by identifying novel epigenetically deregulated genes potentially involved in lung adenocarcinoma development/progression, and by describing an epigenetic subgroup of lung adenocarcinoma associated with characteristic molecular alterations. Cold Spring Harbor Laboratory Press 2012-07 /pmc/articles/PMC3396362/ /pubmed/22613842 http://dx.doi.org/10.1101/gr.132662.111 Text en © 2012, Published by Cold Spring Harbor Laboratory Press This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/. |
spellingShingle | Research Selamat, Suhaida A. Chung, Brian S. Girard, Luc Zhang, Wei Zhang, Ying Campan, Mihaela Siegmund, Kimberly D. Koss, Michael N. Hagen, Jeffrey A. Lam, Wan L. Lam, Stephen Gazdar, Adi F. Laird-Offringa, Ite A. Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression |
title | Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression |
title_full | Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression |
title_fullStr | Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression |
title_full_unstemmed | Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression |
title_short | Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression |
title_sort | genome-scale analysis of dna methylation in lung adenocarcinoma and integration with mrna expression |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396362/ https://www.ncbi.nlm.nih.gov/pubmed/22613842 http://dx.doi.org/10.1101/gr.132662.111 |
work_keys_str_mv | AT selamatsuhaidaa genomescaleanalysisofdnamethylationinlungadenocarcinomaandintegrationwithmrnaexpression AT chungbrians genomescaleanalysisofdnamethylationinlungadenocarcinomaandintegrationwithmrnaexpression AT girardluc genomescaleanalysisofdnamethylationinlungadenocarcinomaandintegrationwithmrnaexpression AT zhangwei genomescaleanalysisofdnamethylationinlungadenocarcinomaandintegrationwithmrnaexpression AT zhangying genomescaleanalysisofdnamethylationinlungadenocarcinomaandintegrationwithmrnaexpression AT campanmihaela genomescaleanalysisofdnamethylationinlungadenocarcinomaandintegrationwithmrnaexpression AT siegmundkimberlyd genomescaleanalysisofdnamethylationinlungadenocarcinomaandintegrationwithmrnaexpression AT kossmichaeln genomescaleanalysisofdnamethylationinlungadenocarcinomaandintegrationwithmrnaexpression AT hagenjeffreya genomescaleanalysisofdnamethylationinlungadenocarcinomaandintegrationwithmrnaexpression AT lamwanl genomescaleanalysisofdnamethylationinlungadenocarcinomaandintegrationwithmrnaexpression AT lamstephen genomescaleanalysisofdnamethylationinlungadenocarcinomaandintegrationwithmrnaexpression AT gazdaradif genomescaleanalysisofdnamethylationinlungadenocarcinomaandintegrationwithmrnaexpression AT lairdoffringaitea genomescaleanalysisofdnamethylationinlungadenocarcinomaandintegrationwithmrnaexpression |