Chapter category: DNA
DNA Hypo- vs. Hypermethylation in Cancer: Tumor Specificity, Tumor Progression, and Therapeutic Implications
DNA Methylation and Cancer Therapy
Edited by: Moshe SzyfISBN: 0-306-47848-X
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Chapter authors:
Melanie Ehrlich and Guanchao Jiang
DNA hypomethylation associated with cancer is probably as frequent as cancer-linked DNA hypermethylation. The hypomethylation of genomic sequences often exceeds hypermethylation so that cancers frequently display lower levels of genomic 5-methylcytosine than do a variety of normal postnatal tissues. Different types of sequences are generally targeted for cancer-related decreases and increases in DNA methylation. Some sequences appear to be more frequently hypomethylated in certain types of cancers than other types. DNA hypomethylation sometimes is evident early in tumorigenesis; however, it also can be associated with tumor progression. Hypomethylation of specific DNA sequences, especially DNA repeats, may serve as a marker for tumorigenesis or tumor progression, as can hypermethylation of unique DNA sequences. Cancer-linked DNA hypomethylation can occur without an association with DNA hypermethylation. Because of this finding and the very frequent targeting of DNA sequences for this hypomethylation in diverse cancers, genomic hypomethylation is likely to contribute to carcinogenesis and not to be just a byproduct of oncogenic transformation. Therefore, caution should be used in development of treatment schemes for cancer involving DNA demethylation because they might result in increased tumor progression.
Additional chapters from this book:
Anticancer Gene Therapy by in Vivo DNA Electrotransfer of MBD2 Antisense
Pascal Bigey and Daniel Scherman
Harnessing the full therapeutic potential of DNA methylation machinery proteins would require efficient techniques of introducing either anti sense, iRNA or expression vectors into tumors in vivo. E...
Preclinical and Clinical Studies on 5-Aza-2'-Deoxycytidine, a Potent Inhibitor of DNA Methylation, in Cancer Therapy
Richard L. Momparler
The preclinical and clinical investigations by the author on the antineoplastic activity of 5-Aza-2'-deoxycytidine (5AZA), a potent inhibitor of DNA methylation are reviewed. These include studies o...
DNA Methyltransferase Inhibitors: Paving the Way for Epigenetic Cancer Therapeutics
Gregory K. Reid and A. Robert MacLeod
Our increased understanding of the molecular pathophysiology of cancer is beginning to impact our ability to effectively treat this disease. The recent success of the tyrosine kinase inhibitor Gleev...
Purine Analogues and Their Role in Methylation and Cancer Chemotherapy
Katherine L. Seley and Sylvester L. Mosley
Despite promising leads in the search for new chemotherapeutic agents, there remains an urgent need to develop more effective and less toxic drugs. Nucleosides and their corresponding nucleobases ar...
The Role of Active Demethylation in Cancer and Its Therapeutic Potential
Moshe Szyf, Paul M. Campbell, Nancy Detich, Jing Ni Ou, Stefan Hamm and Veronica Bovenzi
Regional hypermethylation and global hypomethylation coexist in cancer cells. Understanding the mechanisms responsible for global hypomethylation and regional hypermethylation in cancer is required ...
Inhibition of Poly(ADP-Ribosyl)ation Allows DNA Hypermethylation
Anna Reale, Giuseppe Zardo, Maria Malanga, Jordanka Zlatanova and Paola Caiafa
This chapter emphasizes that along the chain of events that induce DNA methylation-dependent chromatin condensation, a post-synthetic modification other than histone acetylation, poly(ADP-ribosyl)at...
Regulation of DNA Methyltransferases in Cancer
Nancy Detich and Moshe Szyf
The DNA methyltransferases (DNMTs) are critical proteins involved in establishing proper control of epigenetic information. They are responsible for maintaining the cell’s methylation pattern, as we...
Methylation Analysis in Cancer: (Epi)Genomic Fast Track from Discovery to Clinical Routine
Carolina Haefliger, Sabine Maier and Alexander Olek
Aberrant DNA methylation is an early and common event in human cancers. Methylation acts as an epigenetic regulator of gene expression and is involved in cancer development as well as resistance to ...
Identifying Clinicopathological Association of DNA Hypermethylation in Cancers Using CpG Island Microarrays
Susan H. Wei, Timothy T.-C. Yip, Chuan-Mu Chen and Tim H.-M. Huang
Hypermethylation of promoter CpG islands has been associated with gene silencing in cancer. Increasingly, these CpG islands have potential clinical utility as molecular markers for cancer diagnosis....
The Loss of Methyl Groups in DNA of Tumor Cells and Tissues: The Immunochemical Approach
Alain Niveleau, Chandrika Piyathilake, Adriana de Capoa, Claudio Grappelli, Jean-Marc Dumollard, Lucien Frappart and Emmanuel Drouet
The existence of 5-methyldeoxycytidine (5-MeCyd) has been first demonstrated in 1958.1 For several years the presence of this naturally modified base in DNA remained unexplained and its role was ign...
CpG Island Hypermethylation of Tumor Suppressor Genes in Human Cancer: Concepts, Methodologies and Uses
Michel Herranz and Manel Esteller
Aberrations in the DNA methylation patterns are nowadays recognized as a hallmark of human cancer. One of the most characteristic changes is the hypermethylation of CpG islands of tumor suppressor g...
DNA Methylation in Colorectal Cancer
Jeremy R. Jass, Vicki L.J. Whitehall, Joanne Young and Barbara A. Leggett
In this chapter, it is pointed out that colorectal cancer is a heterogeneous disease. The case is made for a ‘serrated pathway’ of neoplasia that would evolve relatively rapidly through the early ac...
DNA Methylation in Urological Cancers
Wolfgang A. Schulz and Hans-Helge Seifert
Urological cancers are a diverse group with different alterations of DNA methylation. In all urological cancers, DNA hypermethylation of specific genes has been described. In contrast, methylation o...
DNA Hypo- vs. Hypermethylation in Cancer: Tumor Specificity, Tumor Progression, and Therapeutic Implications
Melanie Ehrlich and Guanchao Jiang
DNA hypomethylation associated with cancer is probably as frequent as cancer-linked DNA hypermethylation. The hypomethylation of genomic sequences often exceeds hypermethylation so that cancers freq...
Epigenetic Mechanisms of Gene Regulation: Relationships between DNA Methylation, Histone Modification, and Chromatin Structure
Keith D. Robertson
DNA methylation is a post-replicative, or epigenetic, modification of the genome that is critical for proper mammalian embryonic development, gene silencing, X chromosome inactivation, and imprintin...
DNA Methylation: Three Decades in Search of Function
Aharon Razin
DNA methylation is an epigenetic mark that is involved in control mechanisms of a variety of biological processes. Being symmetrically positioned on the two complementary DNA strands the methyl grou...
