Interplay of Epigenetics with Gynecological Cancer

Abstract

Recent data on the cell deregulation that occurs during the progression to cancer underlines the cooperation between genetic and epigenetic alterations leading to a malignant phenotype. Unlike genetic alterations, the epigenetic changes do not affect the DNA sequence of the genes, but determine the regulation of gene expression acting upon the genome. Moreover, unlike genetic changes, epigenetic ones are reversible, making them therapeutic targets in various conditions in general and in cancer disease in particular. The term epigenetics includes a series of covalent modifications that regulate the methylation pattern of DNA and posttranslational modifications of histones. Gene expression can also be regulated at the posttranscriptional level by microRNAs (miRNAs), a family of small noncoding RNAs that inhibit the translation of mRNA to protein. miRNAs can act as ‘oncomiRs’, as tumor suppressors, or both. In this chapter, we will (1) summarize the current literature on the key processes responsible for epigenetic regulation: DNA methylation, histone modifications and posttranscriptional gene regulation by miRNAs; (2) evaluate aberrant epigenetic modifications as essential players in cancer progression; (3) establish the roles of microenvironment-mediated epigenetic perturbations in the development of gynecological neoplasia; (4) evaluate epigenetic factors involved in drug resistance

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