How to stomach an epigenetic insult: the gastric cancer epigenome

Gastric cancer is a deadly malignancy afflicting close to a million people worldwide. Patient survival is poor and largely due to late diagnosis and suboptimal therapies. Disease heterogeneity is a substantial obstacle, underscoring the need for precision treatment strategies. Studies have identifie...

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Bibliographic Details
Published inNature reviews. Gastroenterology & hepatology Vol. 14; no. 8; pp. 467 - 478
Main Authors Padmanabhan, Nisha, Ushijima, Toshikazu, Tan, Patrick
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.08.2017
Subjects
Carcinogenesis
Care and treatment
Cell Transformation, Neoplastic
Development and progression
DNA methylation
Epigenesis, Genetic - genetics
Epigenetic inheritance
Epigenetics
Gastric cancer
Gene expression
Gene Expression Regulation, Neoplastic
Genetic aspects
Genomes
Genotypes
Health aspects
Humans
Malignancy
Molecular Targeted Therapy
Stomach cancer
Stomach Neoplasms - drug therapy
Stomach Neoplasms - genetics
Tumors
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Summary:Gastric cancer is a deadly malignancy afflicting close to a million people worldwide. Patient survival is poor and largely due to late diagnosis and suboptimal therapies. Disease heterogeneity is a substantial obstacle, underscoring the need for precision treatment strategies. Studies have identified different subgroups of gastric cancer displaying not just genetic, but also distinct epigenetic hallmarks. Accumulating evidence suggests that epigenetic abnormalities in gastric cancer are not mere bystander events, but rather promote carcinogenesis through active mechanisms. Epigenetic aberrations, induced by pathogens such as Helicobacter pylori, are an early component of gastric carcinogenesis, probably preceding genetic abnormalities. This Review summarizes our current understanding of the gastric cancer epigenome, highlighting key advances in recent years in both tumours and pre-malignant lesions, made possible through targeted and genome-wide technologies. We focus on studies related to DNA methylation and histone modifications, linking these findings to potential therapeutic opportunities. Lessons learned from the gastric cancer epigenome might also prove relevant for other gastrointestinal cancers.
ISSN:1759-5045
1759-5053
DOI:10.1038/nrgastro.2017.53