Research Progress of DNA Methylation in Endometrial Cancer

Abstract

Endometrial cancer (EC)) is one of the most common malignant tumors of the female genital system, with an increasing incidence and mortality, worldwide. Although the therapeutic strategy of EC is still complicated and challenging, further understanding of carcinogenesis from a gene perspective would allow an effort to improve therapeutic precision in this complex malignancy. DNA methylation is the most widely studied epigenetic alteration in human tumors. Aberrant DNA methylation events, resulting in altered gene expression, are features of many tumor types. In this review, we provide an update on evidence about the roles of aberrant DNA methylation within some classical tumor suppressor genes and oncogenes in endometrial carcinogenesis, and report on recent advances in the understanding of the contribution of aberrant DNA methylation to EC, as well as opportunities and challenges of DNA methylation in EC management and prevention.

SIM2: Its Prognostic Significance and Oncogenic Role in Endometrial Carcinoma

“… 29 Aberrant DNA methylation events have been reported for numerous tumor suppressor genes and oncogenes. 30 For instance, significant contributions of DNA methylation have been noted for genes such as PTEN , 31 RASSF1A 32 and BMP 33 in the context of endometrial carcinogenesis. Here, we uncovered that SIM2 methylation was inversely associated with its mRNA expression, despite that SIM2 promoter methylation level was higher in UCEC samples.…”

Epigallocatechin Gallate for the Treatment of Benign and Malignant Gynecological Diseases—Focus on Epigenetic Mechanisms

“…Possible epigenetic mechanisms of endometrial cancer development and potential therapeutic targets have been recently reviewed [ 223 , 224 ]. The decreased promoter methylation frequency of VEGF, TNF, and HIF1α genes related to increased gene expression was noticed in endometrial cancer tissues as compared to a control study group [ 224 , 225 ]. Furthermore, genes frequently silenced by DNA promoter methylation in endometrial carcinoma were involved in DNA repair: MGMT and hMLH1 [ 226 ].…”

A tale of two pathways: Review of immune checkpoint inhibitors in DNA mismatch repair‐deficient and microsatellite instability‐high endometrial cancers

“…30,39,40 This involves assessment of DNA hypermethylation at the CpG islands in the promoter region. 41,42 However, there have been rare reports of MLH1 promoter hypermethylation in those with MLH1-associated LS, where the methylation serves as a "second hit" in tumor development. 43 Constitutional methylation of MLH1 is also a rare but important mechanism of LS to recognize.…”

“…Given the high accuracy and low costs of IHC, this is usually the first step, followed by MLH1 methylation testing and then LS testing in cases lacking MLH1 promoter hypermethylation 30,39,40 . This involves assessment of DNA hypermethylation at the CpG islands in the promoter region 41,42 . However, there have been rare reports of MLH1 promoter hypermethylation in those with MLH1 ‐associated LS, where the methylation serves as a “second hit” in tumor development 43 .…”