دانلود رایگان مقاله انگلیسی مقایسه تکنیک های تجزیه و تحلیل گسترده ژنوم به تجزیه و تحلیل متیلاسیون DNA در سرطان انسان - وایلی 2017

Abstract

DNA methylation was the first epigenetic modification to be detected in human cancers with specific relation to aberrant gene expression. Herein, DNA methylation analysis explains how epigenetic patterns affect gene expression level. Hypermethylation at tumor suppressor gene loci leads to increased tumorigenesis due to tumor suppressor gene silencing, whereas global hypomethylation of CpG islands (CGIs) is followed by genomic instability and aberrant activation of multiple oncogenes. Therefore, characterization of the genes which silenced or activated epigenetically in human tumor cells can improve our understanding of cancer biology. Different genome-wide methodologies are applied to evaluate methylation status. Various commonly conducted techniques for this evaluation are reviewed in this paper. We provided comparative description of the procedures, advantages, and drawbacks of genome-wide DNA methylation analysis methods and biological applications, to give information on selecting the appropriate method for different methylation studies. This article is protected by copyright.

5. Conclusion

Human cancer is a complex genetic and epigenetic disease. Unlike non- reversible mutagenic events, reversible epigenetic alterations can be considered as potential diagnostic markers and therapeutic targets for cancer therapy [134, 135]. One of the most important epigenetic events in human cancer is aberrant DNA methylation which is known to regulate gene-expression [136]. The genome-wide analysis technologies provide a better understanding of how changes in DNA methylation affect tumor growth and invasiveness. In this review, the common approaches for genome-scale DNA methylation mapping were investigated and the procedure and applications of each method were discussed. The currently applied methods are predominantly performed based upon restriction endonuclease digestion, affinity enrichment and sodium bisulfite conversion, combined with sequencing or array- based methods. The application of each approach depends on the scientific question, power and facility of the method, expected changes in the level of methylation, amount of required DNA, run time and cost [137].