title: DNA methylation and RNA expression profiles in lung adenocarcinomas of never-smokers.
abstract: 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.
authors: Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, MN, USA.
authors: Aaron S
authors: AS
authors: Mansfield
authors: Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Liang
authors: L
authors: Wang
authors: Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Medical Genome Facility, Mayo Clinic, Rochester, MN, USA.
authors: Julie M
authors: JM
authors: Cunningham
authors: Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Medical Genome Facility, Mayo Clinic, Rochester, MN, USA; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors: Jin
authors: J
authors: Jen
authors: Medical Genome Facility, Mayo Clinic, Rochester, MN, USA.
authors: Christopher P
authors: CP
authors: Kolbert
authors: Division of Biomedical Statistics and Informatics, Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors: Zhifu
authors: Z
authors: Sun
authors: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA; Division of Epidemiology and Department of Medical Genetics, Health Sciences Research, Mayo Clinic, Rochester, MN, USA. Electronic address: yang.ping@mayo.edu.
authors: Ping
authors: P
authors: Yang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D025341:Principal Component Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D012907:Smoking / Q000235:genetics*
chemical_list: D012333:RNA, Messenger
keywords: Cell cycle; DNA methylation; epigenetics; gene expression; homeobox; lung adenocarcinoma
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