Epigenetic Mechanisms in Gynecological Cancer

Abstract

The disruption of epigenetic regulatory mechanisms has been demonstrated to represent the prevalent carcinogenetic actor in cancer, aberrant epigenetic silencing of tumor suppressor genes, mainly due to DNA methylation, representing a relevant mechanism able of modifying the expression of key genes during carcinogenesis. In addition, epigenetic regulation has included microRNAs that regulate gene expression leading to inhibition and/or degradation of RNA target. In recent years, epigenetic silencing has been indicated as one of the major causes of gynecological cancer, being able to inactivate multiple pathways including cell cycle control, DNA repair, and apoptosis. In this chapter, the most important environmental factors interfering with the DNA methylation status in mammalian cells, leading to the insurgence of gynecological tumors will be discussed, including the dietary habits that have been indicated as main actors of DNA methylation. The role of epigenetics in the insurgence of ovarian cancer, endometrial cancer, cervical cancer, and endocervical cancer will be discussed. Finally, the role of microbioma in gynecological cancer insurgence and progression will be discussed. Here, a modern view of the relationship between genetics and epigenetics in gynecological cancer is presented. According to this view, genetics might be seen as a piano, a long one with a keyboard of 25,000 keys each one representing one human gene, whereas epigenetics could be represented by the piano tuner and by the pianist. The epigenetic approach is based on changing the pianist, i.e. the hyper-or hypomethylation status of target genes appears much more promising for the therapy of gynecological cancer than the previous ones based on modifying the piano, i.e. the genetic changes accumulating in tumor cells.