Cancer genomics identifies disrupted epigenetic genes

Abstract

Latest advances in genome technologies have greatly advanced the discovery of epigenetic genes altered in cancer. The initial single candidate gene approaches have been coupled with newly developed epigenomic platforms to hasten the convergence of scientific discoveries and translational applications. Here, we present an overview of the evolution of cancer epigenomics and an updated catalog of disruptions in epigenetic pathways, whose misregulation can culminate in cancer. The creation of these basic mutational catalogs in cell lines and primary tumors will provide us with enough knowledge to move diagnostics and therapy from the laboratory bench to the bedside.

Anticancer Natural Compounds as Epigenetic Modulators of Gene Expression

“…Accumulating evidence from the global genome sequencing and expression studies emphasizes the role for genetic and epigenetic alterations leading to inactivation of cancer suppressor genes, overexpression of oncogenes, modification and modulation of transcription factors, chromatin and epigenetic regulators leading to a deregulation of multiple intracellular signaling cascades, and subsequently to cancer development [4, 9, 20, 23, 27, 36]. Because of cancer heterogeneity, new layers of regulation have been added into a complex molecular network leading to carcinogenesis and cancer progression [6].…”

“…Recently, epigenetic DNA and protein post-translational modifications (PTM, e.g. phosphorylation, acetylation, methylation) were shown to largely contribute to the initiation and progression of cancer [12, 20, 21, 23]. On the one hand, a hypermethylation of specific DNA associated with gene promoter regions causes silencing of tumor suppressor genes, leading to inactivation of these genes in cancer cells [10, 14, 16, 20-23, 30, 32-36].…”

Quantitative analysis of ChIP-seq data uncovers dynamic and sustained H3K4me3 and H3K27me3 modulation in cancer cells under hypoxia

“…Well-known examples of histone modifications are trimethylation of histone 3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3), which are often associated with transcriptional activity and repression, respectively. Combined chromatin immunoprecipitation (ChIP) and high-throughput sequencing technology (ChIP-seq [2, 3]) has proven to be a powerful approach to create genome-wide maps of such histone modifications in multiple human cancer cell lines [4–7], and the key to understanding the molecular mechanisms underlying cancer and to improving cancer diagnostics, prognostics and treatment [1, 8, 9]. …”

Investigation of EZH2 pathways for novel epigenetic treatment strategies in oropharyngeal cancer

“…Epigenetic aberrancies involving histone methylation are a hallmark of human cancers [2, 5, 31–34]. Histone methyltransferases, the enzymes that add methylation to histones, are central regulators of gene expression that are often altered in human malignancies.…”

“…Epigenetics relates to any process that alters gene activity without changing the deoxyribonucleic acid (DNA) sequence, and leads to modifications that can be transmitted to daughter cells. These modifications include DNA-methylation, non-coding RNAs and a variety of histone post-translational modifications [5]. Of the later category, histone methylation has been of particular interest for cancer research.…”