Integrated molecular analysis reveals complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas

Dunfa Peng, Yan Guo, Heidi Chen, Shilin Zhao, Kay Washington, Tianling Hu, Yu Shyr, Wael El-Rifai

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Article number40729
JournalScientific Reports
Volume7
DOIs
StatePublished - Jan 19 2017
Externally publishedYes

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Epigenomics
Adenocarcinoma
Gene Expression
Methylation
Genes
Catenins
Gene Regulatory Networks
DNA Methylation
Computational Biology
Interleukin-8
Transcription Factors
DNA
Incidence

ASJC Scopus subject areas

  • General

Cite this

Integrated molecular analysis reveals complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas. / Peng, Dunfa; Guo, Yan; Chen, Heidi; Zhao, Shilin; Washington, Kay; Hu, Tianling; Shyr, Yu; El-Rifai, Wael.

In: Scientific Reports, Vol. 7, 40729, 19.01.2017.

Research output: Contribution to journalArticle

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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.",
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AU - Shyr, Yu

AU - El-Rifai, Wael

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