EPIGENETIC CHANGES IN BREAST CANCER AND OVARIAN CANCER PART I MECHANISMS OF EPIGENETIC CHANGES

The term epigenetic defines a heritable modifications in the genetic material affecting its expression and without any changes in the nucleotide sequences in DNA. These epigenetic changes are based on biochemical reactions at the level of DNA, and the histones as well. Epigenetic modifications of DNA are limited to changes in its level of methylation, while histones modifications relate to the reactions of methylation, acetylation, phosphorylation, sumoylation, ubiquitination or ADP-ribosylation and all reverse reactions. In addition to genomic DNA. epigenetic modifications also include mitochondrial DNA. An important mechanism regulating gene activity at post-transcriptional and post-translational level is the non-coding RNAs eg. microRNA (miRNA). Changes at the epigenetic level with the accumulation of irreversible mutations in the genetic material play an important role in the formation and progression of cancers, including the etiology of breast and ovarian cancers. Modifications at the genetic level that cause tumor growth mainly refer to two groups of genes: proto-oncogenes and suppressor genes. Oncogenes, mutated protoonogenes, contribute to uncontrolled proliferation, while suppressor genes' protein products inhibit cell proliferation. Analysis and characterization of epigenetic changes typical of these tumors can be a potential point of therapy. Applying the methylation reversal strategies within promoter regions of suppressor genes by the use of DNA methyltransferase inhibitors can restore the expression of important regulatory genes and thus affect the cell phenotype.