The Degree of Global DNA Hypomethylation in Peripheral Blood Correlates with That in Matched Tumor Tissues in Several Neoplasia
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There are no good blood and serum biomarkers for detection, follow up, or prognosis of brain tumors. However, they are needed for more detailed tumor classification, better prognosis estimation and selection of an efficient therapeutic strategy. The aim of this study was to use the epigenetic changes in DNA of peripheral blood samples as a molecular marker to diagnose brain tumors as well as other diseases. We have applied a very precise thin-layer chromatography (TLC) analysis of the global amount of 5-methylcytosine (m5C) in DNA from brain tumors, colon and breast cancer tissues and peripheral blood samples of the same patients. The m5C level in tissue DNA from different brain tumor types, expressed as R coefficient, changes within the range of 0.2–1.6 and overlaps with R of that of blood samples. It negatively correlates with the WHO malignancy grade. The global DNA hypomethylation quantitative measure in blood, demonstrates a big potential for development of non-invasive applications for detection of a low and a high grade brain tumors. We have also used this approach to analyze patients with breast and colon cancers. In all these cases the m5C amount in DNA cancer tissue match with data of blood. This study is the first to demonstrate the potential role of global m5C content in blood DNA for early detection of brain tumors and others diseases. So, genomic DNA hypomethylation is a promising marker for prognosis of various neoplasms as well as other pathologies.Keywords:
Brain tumor
RNA-Directed DNA Methylation
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Introduction and Aim: The DNA methylation is involved in the regulation of gene activity and abnormal DNA methylation is associated with various diseases, including cancer. MAP9 (Microtubule-Associated Protein 9) gene methylation was investigated as a potential epigenetic biomarker for cancer in this work. The results were published in Cancer Research. Materials and Methods: The present study was on 40 breast cancer samples and 20 healthy samples to identify diagnosis biomarkers for breast cancer. DNA was extracted from the whole blood of breast cancer patients and healthy samples and were converted to bisulfite by using EpiTect Fast DNA Bisulfite Kit –Part 1 from Qiagen company. Then used Qia gene methylation kit to identify methylated site an epigenetic marker (MAP9) using HRM software in RT-PCR. Results: The findings of the present investigation revealed that the methylation of the MAP9 gene in breast cancer patients were 28 (70%) compared to healthy patients 2 (10%) at a significant difference (P<0.01). Conclusion: The MAP9 gene is hypermethylated in breast cancer patients, and it has the potential to be exploited as a molecular biomarker for the detection of breast cancer.
Bisulfite sequencing
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Dinoflagellate
Epigenesis
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Abstract Transient nutritional exposures during critical ontogenic periods can cause persistent changes in gene expression, metabolism, and risk of various diseases including cancer. We have been investigating whether such ‘developmental programming’ occurs via nutritional influences on developmental epigenetics. Our studies in agouti viable yellow and axin fused mice showed that developmental establishment of DNA methylation at ‘metastable epialleles’ is especially sensitive to maternal nutritional status around the time of conception. Lately, using a multiple-tissue screen for interindividual variation in DNA methylation, we have identified human genomic regions that appear to be metastable epialleles. Stochastic establishment of DNA methylation at these loci is affected by maternal nutrition around the time of conception, consistent across multiple tissues, and stable for many years. Most recently, our studies using genome-wide bisulfite sequencing have identified candidate metastable epialleles that are associated with genes implicated in human cancer, potentially providing opportunities for cancer risk assessment and prevention. Citation Format: Robert A. Waterland. Nutrition, epigenetics, and cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PL02-01.
Genomic Imprinting
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Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Early detection of CRC can significantly reduce this mortality rate. Unfortunately, recommended screening modalities, including colonoscopy, are hampered by poor patient acceptance, low sensitivity and high cost. Recent studies have demonstrated that colorectal oncogenesis is a multistep event resulting from the accumulation of a variety of genetic and epigenetic changes in colon epithelial cells, which can be reflected by epigenetic alterations in blood. DNA methylation is the most extensively studied dysregulated epigenetic mechanism in CRC. In this review, we focus on current knowledge on DNA methylation as potential blood-based biomarkers for early detection of CRC.
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Colotectal cancer arises as a consequence of the accumulation of genetic and epigenetic alterations in colonic mucous epithelial cells.Epigenetic changes,particularly DNA methylation is recognized as common molecular alterations in human tumors.It may be used as colorectal cancer detection or prognosis markers.In this review,we summarized the characteristics of epigenetic changes and clinical applications in colorectal cancer.
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AbstractThe discovery of a family of highly conserved DNA cytosine methylases in honey bees and other insects suggests that, like mammals, invertebrates possess a mechanism for storing epigenetic information that controls heritable states of gene expression. Recent data also show that silencing DNA methylation in young larvae mimics the effects of nutrition on early developmental processes that determine the reproductive fate of honey bee females. We evaluate the impact of these findings on future studies of environmentally-driven phenotypic plasticity in social insects, and discuss how they may help in understanding the nutritional basis of epigenetic reprogramming in humans.
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