Commonly integrated epigenetic modifications of differentially expressed genes lead to adaptive resistance in cancer.

Publication Title

Epigenomics

Authors

Abdullah Al Emran
Diego M Marzese, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, USAFollow
Dinoop R Menon, Department of Translational Molecular Medicine, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404, USA.
Heinz Hammerlindl
Farzana Ahmed
Erika Richtig
Pascal Duijf
Dave Hoon, Department of Translational Molecular Medicine, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404, USA.Follow
Helmut Schaider

Document Type

Article

Publication Date

5-1-2019

Keywords

Cell Line, Tumor; DNA Methylation; Down-Regulation; Drug Resistance, Neoplasm; Drug Tolerance; Gene Expression Profiling; Histones; Humans; Insulin-Like Growth Factor Binding Protein 5; Neoplasms; Promoter Regions, Genetic; Survival Analysis

Abstract

Aim: To investigate the integrated epigenetic regulation of acquired drug resistance in cancer. Materials & methods: Our gene expression data of five induced drug-tolerant cell models, one resistant cell line and one publicly available drug-resistant dataset were integrated to identify common differentially expressed genes and pathways. ChIP-seq and DNA methylation by HM450K beadchip were used to study the epigenetic profile of differential expressed genes. Results & conclusion: Integrated transcriptomic analysis identified a common 'viral mimicry' related gene signature in induced drug-tolerant cells and the resistant state. Analysis of the epigenetic regulation revealed a common set of down-regulated genes, which are marked and regulated by a concomitant loss of H3K4me3, gain of H3K9me3 and increment of regional DNA methylation levels associated with tumor suppressor genes and apoptotic signaling.

Clinical Institute

Cancer

Specialty/Research Institute

Oncology