Epigenetic roles in the malignant transformation of gastric mucosal cells

Abstract

Gastric carcinogenesis occurs when gastric epithelial cells transition through the initial, immortal, premalignant, and malignant stages of transformation. Epigenetic regulations contribute to this multistep process. Due to the critical role of epigenetic modifications , these changes are highly likely to be of clinical use in the future as new biomarkers and therapeutic targets for the early detection and treatment of cancers. Here, we summarize the recent findings on how epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, regulate gastric carcinogenesis, and we discuss potential new strategies for the diagnosis and treatments of gastric cancer. The strategies may be helpful in the further understanding of epigenetic regulation in human diseases.

Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies

“…Promoter hypermethylation of several tumor suppressor genes has been correlated with gastric cancer susceptibility [ 17 ]. The literature reports many genes significantly hypermethylated in cancer tissue compared with normal tissue of GC subjects [ 18 – 20 ], but relatively few studies have reported DNA methylation markers for early detection [ 21 – 24 ].…”

“…H. pylori infection has been correlated with the progressive accumulation of epigenetic alterations in gastric mucosa [ 17 ]. Promoter hypermethylation in specific tumor suppressor genes has been associated with H. pylori infection in the multistep carcinogenetic process by several groups [ 27 , 28 ].…”

Identification of different mutational profiles in cancers arising in specific colon segments by next generation sequencing

“…Epigenetic alterations play a pivotal role in the inactivation of tumor suppressor genes and activation of oncogenes in a wide spectrum of tumors including CRC. Alteration of the chromatin status is known to be an early event during the malignant transformation of colonic epithelial cells [ 41 ]. Notably, MLL2 and MLL3 are methyl-transferases that methylate the Lys-4 position of histone H3 and thus represent key transcriptional regulators that are essential for cell differentiation, embryonic development, cell fate transition [ 42 ] metabolism [ 43 ] and tumor suppression [ 44 ].…”

Antibiotic Sensitivity to Helicobacter pylori Growth

“…During the early phases of oxyntic gastritis caused by H. pylori, gastric acid secretion may be only moderately reduced and H. pylori eradication even in patients with some degree of atrophy can augment acid secretion (Tie et al, 2016). In patients with pangastritis and oxyntic atrophy, H. pylori may not be detectable.…”