This book is a comprehensive survey of new and exciting developments regarding the role of DNA methylation in human cancer. Issues related to the mutagenicity of 5-methylcytosine and the increase in the interaction of chemical and physical carcinogens with these residues is discussed. The book summarizes the modulation of viral gene expression and the silencing of tumor suppressor genes and illustrates mechanisms by which the methylation signal is translated into altered chromatin structure. The relationship between DNA methylation and genomic imprinting and cancer, and changes in CpG island methylation which occur in aging are discussed. Mouse model systems have played a key role in our dissection of the relationship between methylation and cancer, and these are also portrayed together with descriptions of new clinical trials in which methylation inhibitors are being used to treat leukemia, myeloid dysplastic syndromes and hemoglobinopathies.
List of Contents.- Mutation Hotspots and DNA Methylation.- The Role of DNA Methylation in Modulating Epstein-Barr Virus Gene Expression.- Promoter-Region Hypermethylation and Gene Silencing in Human Cancer.- Mammalian Methyltransferases and Methyl-CpG-Binding Domains: Proteins Involved in DNA Methylation.- Relationship Between Transcription and DNA Methylation.- DNA Methylation, Genomic Imprinting and Cancer.- CpG-Island Methylation in Aging and Cancer.- Mouse Models in DNA-Methylation Research.- DNA Methylation Inhibitors in the Treatment of Leukemias, Myelodysplastic Syndromes and Hemoglobinopathies: Clinical Results and Possible Mechanisms of Action.