DNA Hypermethylation in Breast Cancer

Abstract

Cancer development is a complex process with multiple steps. Many factors, including radiation, chemicals, viruses, genetic and epigenetic changes, lead to abnormal proliferation of a single cell, which results in the outgrowth of a population of clonal-derived tumour cells. It has established that DNA hypermethylation, an epigenetic mechanism that occurred by the addition of a methyl group at 5′ position of the pyrimidine ring of cytosine residues at CpG islands through the action of DNA methyltransferase enzymes, has been considered as the cause of human tumorigenesis, including breast cancer development. Moreover, DNA hypermethylation holds a promising application as a potential biomarker for the early detection, prognosis and prediction of drug sensitivity in cancer. Therefore, this chapter focuses on the description and exempliication of the DNA hypermethylation changes, particularly, highlight the DNA hypermethylation as a potential biomarker applied in predictive, diagnostic, prognostic and therapeutic monitoring of breast cancer.

The epigenetic role of breastfeeding in mammary differentiation

“…It is important to note that the changes observed in methylation were analyzed in non-tumoral mammary gland, which differs from the hypermethylation processes observed in pre-tumor or tumor tissues. 47 This would explain why the differences between the different groups in the levels of methylation are not all-or-nothing responses.…”

Curcumin as an anti-proliferative agent in breast cancer through RassF1a, Bax, and caspase-3 protein

“…Hypermethylation is reversible, and it is possible to re-express hypermethylated genes in cancer with demethylation drugs, so that the tumor suppressor genes that were previously inactive can be regulated and their function be improved. The administration of demethylation drugs in the tumor cell lines causes the reactivation of the tumor suppressor function, but demethylation drugs have side effects that limit the dose and duration of the treatment and have the potential to form mutagenic lesions [4,7,8]. Therefore, the use of new compounds from natural substances that can affect epigenetic changes and have low toxicity to inhibit the development of cancer cells is an important field of cancer treatment research.…”

Promoter Hypermethylation of Tumor Suppressor Genes Located on Short Arm of the Chromosome 3 as Potential Biomarker for the Diagnosis of Nasopharyngeal Carcinoma

“…Unlike genetic mutation, epigenetic alterations can be reversed to their normal state, thereby making such initiatives promising therapeutic biomarkers [4]. DNA methylation, which is the most common epigenetic alteration, is a covalent modification of 5 cytosine located at a CpG dinucleotide by adding a methyl group in the 5th carbon of the ring using S-adenosyl methionine as a methyl donor [4,9,10]. The alterations of DNA hypermethylation in the promoter region or the first exon of the tumor suppressor gene (TSG) lead to its inactivation.…”