Application of DNA methylation biomarkers for endometrial cancer management

Abstract

It has become clear that aberrant gene expression, via alterations in promoter methylation or histone acetylation, is a contributing factor for carcinogenesis, perhaps as important as genetic mutation. This is particularly evident in endometrial cancer, in which multiple genes are silenced through hypermethylation. In this review, we discuss the field of epigenetics and relevant techniques to characterize methylation and acetylation alterations. The CpG island methylator phenotype, epimutations and the effects of aging on methylation are also discussed. In endometrial cancer there is evidence that hypermethylation of relevant genes can be reversed using epigenetic inhibitors, resulting in re-expression of silenced genes. Preliminary data also suggest that a panel of methylation biomarkers could be useful for diagnosis and even screening in selected populations at high risk. This disease is particularly well suited for such a strategy given that the endometrium is readily accessible for testing and endometrial cancer precursors are well defined.

Keywords::

• biomarker
• cancer diagnosis
• cancer treatment
• DNA methylation
• endometrial cancer
• epigenetics
• intravaginal tampons

Financial & competing interests disclosure

Shi-Wen Jiang is the Distinguished Cancer Scholar supported by the Georgia Cancer Coalition. This work is partially funded by the grant National Institutes of Health (NIH) R01 HD 41577 (Shi-Wen Jiang), NIH/National Cancer Institute (NCI) MD Anderson Uterine Cancer SPORE (Shi-Wen Jiang, Jinping Li), Gynecologic Cancer Foundation (Sean C Dowdy, Shi-Wen Jiang), the Fraternal Order of Eagles Cancer Research Award (Sean C Dowdy, Shi-Wen Jiang), NIH Clinical Investigator Loan Repayment Program (Sean C Dowdy), NIH K12 training program (Sean C Dowdy, Shi-Wen Jiang) and research supplement from the Mercer University School of Medicine (Shi-Wen Jiang, Jinping Li).

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.