Department of Biochemistry and Molecular Biology, University of Florida,
Gainesville, Florida, USA
Department of Infectious Diseases & Pathology, College of Veterinary Medicine, University of Florida
In the last three decades, epigenetic alterations have been distinguished in three different epigenetic systems, which interact with each other: DNA methylation, histone modification and RNA-associated silencing. DNA methylation is a chemical modification of cytosine in the CG dinucleotide characterized by the addition of a methyl group at the 5- carbon position of the cytosine pyrimidine ring, and it has been recognized after its discovery playing a key role in tumorigenesis.
The cis-regulatory elements in front of each gene promoter consist of characteristic DNA sequence as the binding sites for different factors. In most instances the hypermethylated DNA blocks the activation of transcription factors and enzymes, which suppress the activity of the neighbor gene. This epigenetic phenomenon largely determines which genes in a tissue or a cell are expressed. Tumor cells often exhibit methylation patterns that differ significantly from those of healthy tissues. Thereby a tumor may be associated with both strong methylations (hypermethylation) of upstream DNA regions, as well as with a reduced degree of methylation (hypomethylation). Methylation in the promoter region of a gene is typically associated with suppression of transcription of the associated gene. It has been also shown that DNA methylation plays a central role in a variety of genetic mechanisms, such as the differentiation of various celland tissue types, the suppression of repetitive DNA elements, inactivation of the second X chromosome in women, the selection of the paternal or maternal allele of certain genes and the genetic imprinting caused by environmental influences.
A correlation between methylation of specific genes and tumor recurrence, prognosis, has been shown in prostate cancer, breast cancer and lung cancer. However, it is only a part of genes that have been described, whether it is just the signs of more aggressive tumor markers (prognostic markers) or a pre-existing or developing phenomenon to chemotherapy resistance by tumor (predictive markers) need to be clarified.
Aims and Scope:
1. DNA methylation detection in tissue, plasma, serum, peritoneal fluid, and etc. 2. DNA methylation pattern in various cancer 3. DNA methylation for cancer risk screen 4. DNA methylation for diagnosis 5. DNA methylation for cancer stage monitoring 6. DNA methylation for cancer prognosis 7. DNA methylation for chemotherapy resistance