DNA Methylation and Cancer

Part of the Progress in Drug Research book series (PDR, volume 67)


DNA methylation acts in concert with other epigenetic mechanisms to regulate normal gene expression and facilitate chromatin organization within cells. Aberrant DNA methylation patterns are acquired during carcinogenic transformation; such events are often accompanied by alterations in chromatin structure at gene regulatory regions. The expression pattern of any given gene is achieved by interacting epigenetic mechanisms. First, the insertion of nucleosomes at transcriptional start sites prevents the binding of the transcriptional machinery and additional cofactors that initiate gene expression. Second, nucleosomes anchor all of the DNMT3A and DNMT3B methyltransferase proteins in the cell, which suggests a role for histone octamers in the establishment of DNA methylation patterns. During carcinogenesis, epigenetic switching and 5-methylcytosine reprogramming result in the aberrant hypermethylation of CpG islands, reducing epigenetic plasticity of critical developmental and tumor suppressor genes, rendering them unresponsive to normal stimuli. Here, we will discuss the importance of both established and novel molecular concepts that may underlie the role of DNA methylation in cancer.


Transcriptional Start Site Histone Variant Nucleosome Occupancy DNMT Inhibitor Aberrant Hypermethylation 



We thank Dr. Theresa Kelly, Dr. Fernanda Molognoni, Daniel de Carvalho, and Shikhar Sharma for reviewing the manuscript and their helpful suggestions.


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© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Department of Urology, Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

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