Regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus

Okabe, Atsushi; Funata, Sayaka; Matsusaka, Keisuke; Namba, Hiroe; Fukuyo, Masaki; Rahmutulla, Bahityar; Oshima, Motohiko; Iwama, Atsushi; Fukayama, Masashi; Kaneda, Atsushi

doi:10.1038/s41598-017-08370-7

Cited by 33 publications

(44 citation statements)

References 62 publications

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“…Moreover, not only DNA methylation but also other epigenetic alterations caused by EBV infection may contribute to carcinogenesis. EBV infection causes enhancer activation and repression, which may be associated with gastric carcinogenesis [31]. A recent study suggested that enhancer activation through ATF3 might be involved in carcinogenesis [32].…”

Section: Epigenetic Aberrant In Gastric Cancermentioning

confidence: 99%

DNA Methylation and Genetic Aberrations in Gastric Cancer

et al. 2020

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Background: Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. GC is a pathologically and molecularly heterogeneous disease. DNA hypermethylation in promoter CpG islands causes silencing of tumor-suppressor genes and thus contributes to gastric carcinogenesis. In addition, various molecular aberrations, including aberrant chromatin structures, gene mutations, structural variants, and somatic copy number alterations, are involved in gastric carcinogenesis. Summary: Comprehensive DNA methylation analyses revealed multiple DNA methylation patterns in GCs and classified GC into distinct molecular subgroups: extremely high-methylation epigenotype uniquely observed in GC associated with Epstein-Barr virus (EBV), high-methylation epigenotype associated with microsatellite instability (MSI), and low-methylation epigenotype. In The Cancer Genome Atlas classification, EBV and MSI are extracted as independent subgroups of GC, whereas the remaining GCs are categorized into genomically stable (GS) and chromosomal instability (CIN) subgroups. EBV-positive GC, exhibiting the most extreme DNA hypermethylation in the whole human malignancies, frequently shows CDKN2A silencing, PIK3CA mutations, PD-L1/2 overexpression, and lack of TP53 mutations. MSI, exhibiting high DNA methylation, often has MLH1 silencing and abundant gene mutations. GS is generally a diffuse-type GC and frequently shows CDH1/RHOA mutations or CLDN18–ARHGAP fusion. CIN is generally an intestinal-type GC and frequently has TP53 mutations and genomic amplification of receptor tyrosine kinases. Key Messages: The frequency and targets of genetic aberrations vary depending on the epigenotype. Aberrations in the genome and epigenome are expected to synergistically interact and contribute to gastric carcinogenesis and comprehensive analyses of those in GCs may help elucidate the mechanism of carcinogenesis.

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Section: Epigenetic Aberrant In Gastric Cancermentioning

confidence: 99%

DNA Methylation and Genetic Aberrations in Gastric Cancer

et al. 2020

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“…ChIP-seq analysis was performed as described [20] . ChIP libraries were constructed using NEBNext ChIP-seq Library Prep Reagent Set for Illumina (NEB, Ipswich, MA), quantified using Bioanalyzer (Agilent, Santa Clara, CA), and sequenced at concentration of 4 pM on Illumina Hiseq (Illumina).…”

Section: Methodsmentioning

confidence: 99%

Identification of AR-V7 downstream genes commonly targeted by AR/AR-V7 and specifically targeted by AR-V7 in castration resistant prostate cancer

Sugiura

Sato

Okabe

et al. 2021

Translational Oncology

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Highlights The entire landscape of AR-V7 target regions/genes in CRPC cells was investigated. We identified 78 AR-V7 target genes, targeted specifically by AR-V7 e.g. SLC3A2 , or commonly by AR and AR-V7 e.g. NUP210 . SLC3A2 and NUP210 were markedly upregulated in clinical CRPC tissues, leading to increased proliferation in CRPC.

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“…One outstanding question from these studies is whether clearly distinct GC subsets are characterized by unique regulatory element landscapes. In this regard, Okabe and colleagues demonstrated pro‐oncogenic enhancer dysregulation through redistribution of repressive histone marks following EBV infection in vitro, thereby establishing a potential EBV‐induced enhancer landscape unique to this subtype …”

Section: Multifaceted Molecular Classification Of Gcmentioning

confidence: 99%

Dissection of gastric cancer heterogeneity for precision oncology

Tan

2019

Cancer Science

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Gastric cancer (GC) remains the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. Comprehensive ‐omic studies have unveiled a heterogeneous GC landscape, with considerable molecular diversity both between and within tumors. Given the complex nature of GC, a long‐sought goal includes effective identification of distinct patient subsets with prognostic and/or predictive outcomes to enable tailoring of specific treatments (“precision oncology”). In this review, we highlight various approaches to molecular classification in GC, covering recent genomic, transcriptomic, proteomic and epigenomic features. We pay special attention to the translational significance of classifier systems and examine potential confounding factors which deserve further investigation. In particular, we discuss recent advancements in our knowledge of intra‐subtype, intra‐patient and intra‐tumor heterogeneity, and the pivotal role of the tumor stromal microenvironment.

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Regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus

Cited by 33 publications

References 62 publications

DNA Methylation and Genetic Aberrations in Gastric Cancer

DNA Methylation and Genetic Aberrations in Gastric Cancer

Identification of AR-V7 downstream genes commonly targeted by AR/AR-V7 and specifically targeted by AR-V7 in castration resistant prostate cancer

Dissection of gastric cancer heterogeneity for precision oncology

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