Combinatorial epigenetic deregulation by Helicobacter pylori and Epstein-Barr virus infections in gastric tumourigenesis.
Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodelling and microRNAs, convert environmental signals to transcriptional outputs but are commonly hijacked by pathogenic microorganisms. Recent advances in cancer epigenomics have shed new light on the importance of epigenetic deregulation in Helicobacter pylori- and Epstein-Barr virus (EBV)-driven gastric tumourigenesis. Moreover, it is becoming apparent that epigenetic mechanisms interact through crosstalk and feedback loops, which modify global gene expression patterns. The SWI/SNF remodelling complexes are commonly involved in gastric cancers associated with H. pylori or EBV through different mechanisms, including microRNA-mediated deregulation and genetic mutations. While H. pylori causes epigenetic silencing of tumour-suppressor genes to deregulate cellular pathways, EBV-positive tumours exhibit a widespread and distinctive DNA hypermethylation profile. Given the early successes of epigenetic drugs in haematological malignancies, further studies are mandated to enrich and translate our understanding of combinatorial epigenetic deregulation in gastric cancers into interventional strategies in the clinic. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.|State Key Laboratory of Digestive Diseases, Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.|Shenzhen Research Institute, Chinese University of Hong Kong, Shenzhen, People's Republic of China.
William Kk
WK
Wu
Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.|State Key Laboratory of Digestive Diseases, Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.|Shenzhen Research Institute, Chinese University of Hong Kong, Shenzhen, People's Republic of China.
Jun
J
Yu
Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
Matthew Tv
MT
Chan
Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.|State Key Laboratory of Digestive Diseases, Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
Ka F
KF
To
School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.|State Key Laboratory of Digestive Diseases, Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.|Shenzhen Research Institute, Chinese University of Hong Kong, Shenzhen, People's Republic of China.
Alfred Sl
AS
Cheng
D063646:Carcinogenesis; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000235:genetics / Q000473:pathology / Q000821:virology; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D013274:Stomach Neoplasms / Q000150:complications* / Q000235:genetics / Q000382:microbiology / Q000473:pathology
D035683:MicroRNAs
EBV; Helicobacter pylori; SWI/SNF chromatin remodeller; cancer epigenome; epigenetic therapy; gastric carcinogenesis; promoter hypermethylation