Epigenetic enzymes and their mutations in cancer

Abstract

Epigenetic mechanisms are crucial for normal development and maintenance of tissue-specific gene expression patterns in mammals. Impaired epigenetic processes can cause alterations in gene function and malignant cellular transformation. It is now known that epigenetic abnormalities, together with genetic changes, have a role in the onset and progression of cancer, which was once thought to be a genetic disease. Recent developments in the field of cancer epigenetics have demonstrated substantial reprogramming of all elements of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, and non-coding RNAs. DNA methyltransferases, histone acetyltransferases, and histone deacetylases are a few examples of epigenetic regulatory enzymes that are involved in epigenetic modification. In recent years, an increasing number of studies have demonstrated that mutations in epigenetic regulatory enzymes occur in various cancer types and are closely associated with the malignant phenotype. Hence, research on inhibitors that target these mutant enzymes has gradually shifted into preclinical and clinical stages. In this chapter, we first discuss the epigenetic regulatory enzymes and then how their mutations are associated with carcinogenesis.