Epigenetic link between endometriosis and cancer

Epigenetic modifications propel our understanding of malignant transformation in endometriosis with the potential for early diagnostic interventions and new effective therapies

Key Points

Highlights:

• Although endometriosis is considered benign, it is associated with an increased risk of malignant transformation, with the involvement of various mechanisms of development
• More evidence reveals an important contribution of epigenetic modification mechanisms of endometriosis malignant transformation, including DNA methylation and
  demethylation, histone modifications, and miRNA aberrant expressions

Importance:

• Studying epigenetic modifications of endometriosis will propel our understanding of the pathogenesis of endometriosis malignant transformation, with the potential for early diagnostic interventions and new effective therapies.

What's done here:

• In this review article, the authors have compiled the possible epigenetic mechanisms discovered in the malignant transformation of endometriosis emphasizing the potential research areas.

Data:

• Epigenetics, a heritable modification in gene expression without alteration of DNA sequence. The epigenetic modifications in endometriotic tissue involve:
  • DNA methylation (both addition (hypermethylation) or loss of methyl molecule (hypomethylation) to DNA seems to be important)
  • histone modifications (exert an equivalent effect on epigenetic regulation)
  • noncoding microRNAs (miRNAs) (play role in many processes including cell cycle, apoptosis, proliferation, invasion, and metastasis, and chemoresistance)
• These modifications, in turn, seem to be effective through estrogen and progesterone hormones or causing cellular oxidative stress by forming toxic oxygen molecules (radicals).

Lay Summary

Although endometriosis is considered a benign condition the cellular, histologic, and molecular data strongly demonstrate that endometriosis has neoplastic characteristics. There is strong evidence that endometriosis shares striking features with malignancy like normal tissue dissemination, invasion, and organ damage, as well as new vessel formation (neoangiogenesis). 

In the review entitled "Endometriosis malignant transformation: Epigenetics as a probable mechanism in ovarian tumorigenesis", recently published in the International Journal of Genomics, Jiaxing et al from China, summarize specifically the research concerning the relationship between endometriosis and ovarian cancer and epigenetic modifications. Authors aimed not only to summarize the epigenetic modifications of the relations between endometriosis malignant transformation to ovarian cancer, but also they talked about the potential correlations between them by relevant literature. 

Association between endometriosis and ovarian cancer was reported for the first time as early as 1925 by Dr. J. A. Sampson. Epigenetics is described as a heritable modification in gene expression without alteration of DNA sequence compared with the gene mutation. The epigenetic modifications in endometriotic tissue involve DNA methylation, histone modifications, and noncoding microRNAs (miRNAs). Both addition (hypermethylation) or loss of methyl molecule (hypomethylation) to DNA seems to be important. These modifications, in turn, seem to be effective through estrogen and progesterone hormones or causing cellular oxidative stress by forming toxic oxygen molecules (radicals). 

DNA methylation is the addition of the methyl groups into the cytosines at their carbon-5 position is mediated by a family of enzymes known as the DNA methyltransferases and this heritable epigenetic event significantly regulates gene expression without changing DNA sequence. It is the most frequently studied epigenetic alteration, and the genes which are silenced or activated by DNA methylation, the relation of DNA methylation with the expression of hormone receptors, and oxidative stress which can eliminate or induce specific DNA by regulating related enzymes are important in both endometriosis and endometriosis-related cancers.

Histones are proteins that make up nucleosomes, which are the fundamental unit of the genetic material. Histone modification seems to exert an equivalent effect on epigenetic regulation the same as DNA methylation. Another epigenetic regulation of gene expression has been discovered and well established participating in gene downregulation mediated by small, non-protein-coding RNA molecules named microRNAs (miRNAs). The role of miRNAs is present in different biological processes including cell cycle, apoptosis, proliferation, invasion, and metastasis, and even chemoresistance. 

"Studying epigenetic modifications of endometriosis, as well as investigating the correlation between endometriosis and ovarian cancer, will propel our understanding of the pathogenesis of endometriosis malignant transformation, with the potential for early diagnostic interventions and new effective therapies" added researchers.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29780815