Epigenetic modifications in tumor suppressor genes (TSG): its contribution to tumor development and its clinical relevance

Abstract

Tumor development is the result of genetic and epigenetic alterations. The epigenetic mechanisms do not imply a change in the DNA sequence but can be as important as the genetic mechanisms for the onset and progression of cancer due to its important role in the regulation of gene expression. Methylation and acetylation of histones induce changes in the structure of chromatin that can repress or facilitate the expression of genes. Another epigenetic modification studied in recent years is the methylation of DNA. Recently it has been observed that there are abnormal patterns of DNA methylation in many types of cancers. The malignant cells are accompanied by a global hypomethylation that is associated with the activation of genes required for the invasion and metastasis and a local hypermethylation (CpG Islands) associated with the repression of tumor suppressor genes (TSGs). Thus, the methylation of the TSG blocks its expression, contributing to the onset and tumor progression. Classic examples are the genes BRCA1, PRC, TP53 and PRDM in breast, colon, skin and lung cancer, respectively.The abnormal patterns of DNA methylation, as well as epigenetic modifications on histones, could be used as biomarkers for the diagnosis of cancer and as targets of drugs, in order to correct these alterations and restore the function of the genes. This chapter analyses the current evidence on the role of epigenetic mechanisms involved in the progression of various types of cancer and their clinical relevance.