DNA methylation and RNA expression profiles in lung adenocarcinomas of never-smokers. Cancer Genet 2015 May;208(5):253-60
Date
02/05/2015Pubmed ID
25650174Pubmed Central ID
PMC4465988DOI
10.1016/j.cancergen.2014.12.002Scopus ID
2-s2.0-84930571914 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
Lung cancer occurs in never-smokers. Epigenetic changes in lung cancer potentially represent important diagnostic, prognostic, and therapeutic targets. We compared DNA methylation profiles of 28 adenocarcinomas of the lungs of never-smokers with paired adjacent nonmalignant lung tissue. We correlated differential methylation changes with gene expression changes from the same 28 sample pairs. Using principal component analysis, we observed a distinct separation in methylation profiles between tumor and adjacent nonmalignant lung tissue. Tumors were generally hypomethylated compared with adjacent nonmalignant tissue. Of 1,906 CpG sites differentially methylated between tumor and nonmalignant tissue, 1,198 were within classically defined CpG islands where tumors were hypermethylated compared with nonmalignant tissue. A total of 708 sites were outside CpG islands where tumors were hypomethylated compared with nonmalignant tissue. There were significant differences in expression of 351 genes (23%) of the 1,522 genes matched to the differentially methylated CpG sites. Genes that were not significantly differentially expressed and were hypermethylated within CpG sites were enriched for homeobox genes. These results suggest that the methylation profiles of lung adenocarcinomas of never-smokers and adjacent nonmalignant lung tissue are significantly different. Despite the differential methylation of homeobox genes, no significant changes in expression of these genes were detected.
Author List
Mansfield AS, Wang L, Cunningham JM, Jen J, Kolbert CP, Sun Z, Yang PMESH terms used to index this publication - Major topics in bold
AdenocarcinomaAged
CpG Islands
DNA Methylation
Epigenesis, Genetic
Female
Humans
Lung Neoplasms
Male
Middle Aged
Principal Component Analysis
Promoter Regions, Genetic
RNA, Messenger
Smoking
