Integrated molecular analysis reveals complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas
Year: 2017
Type: article
Abstract: The incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the United States and Western countries. In this study, we carried out an integrative molecular analysis to identify interactions between genomic and epigenomic alterations in regulating gene expression networks in EAC. We detected significant alterations in DNA copy numbers (CN), gene expression levels, and DNA methylation profiles. The integrative analysis demonstrated that altered expression of 1,755 genes was associated with changes in CN or methylation. We found that expression alterations in 84 genes were associated with changes in both CN and methylation. These data suggest a strong interaction between genetic and epigenetic events to modulate gene expression in EAC. Of note, bioinformatics analysis detected a prominent K-RAS signature and predicted activation of several important transcription factor networks, including β-catenin, MYB, TWIST1, SOX7, GATA3 and GATA6. Notably, we detected hypomethylation and overexpression of several pro-inflammatory genes such as COX2, IL8 and IL23R, suggesting an important role of epigenetic regulation of these genes in the inflammatory cascade associated with EAC. In summary, this integrative analysis demonstrates a complex interaction between genetic and epigenetic mechanisms providing several novel insights for our understanding of molecular events in EAC.
Source: Scientific Reports
DOI: 10.1038/srep40729
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: U.S. Department of Veterans Affairs, Vanderbilt University, Georgia Clinical and Translational Science Alliance, National Institutes of Health, Vanderbilt Digestive Diseases Research Center, Vanderbilt University Medical Center, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: G2065299061, G2268269956, G2367676916, G3031895702, G3051419658, G3433274139, G3618326370, G364208108, Molecular Pathobiology of Barrett's Tumorigenesis, G4020890471, G4265562110, The Molecular Functions of APE1 in Barrett's Tumorigenesis, SPORE in GI Cancer, G5679716143, G5853943267, G702371463, G7520984233, The Vanderbilt Institute for Clinical and Translational Research (VICTR), G8543375580, The Role of Aurora Kinase in Upper Gastrointestinal Adenocarcinomas, G8710842620, G9000076948, G9000081609, G9000182424, Molecular and Cellular Basis for Digestive Diseases, Cancer Center Support Grant
OpenAlex ID: W2573366226