Techniques/tools to study epigenetic biomarkers in human cancer detection

Abstract

Epigenetic modifications such as DNA methylation and histone modification are essential for normal developmental process and regulation of tissue-specific gene expression in mammals. However, altered epigenetic processes contributed to change in gene expression and transform cell to malignant type. Global epigenetic changes such as DNA methylation (hypomethylation and hypermethylation), histone modification (acetylation and phosphorylation), and nucleosome repositioning are associated with cancer onset and progression. Expression of several tumour suppressor genes (CDH1, RB, and MLH1), oncogenes (BRCA1 and DAPK), and cell cycle regulatory genes (RB, RASSF1, and P27K1P1) was altered due to epigenetic modification. Several methods have been developed since the last two decades for studying epigenetic modification. Initially, bisulfitebased method was predominantly used for studying DNA modification; however, advancement in techniques led to the development of more robust methods (MeDIP assay, NGS-based method, mass spectrometry, and microarray analysis) for studying whole-genome methylome analysis, while ChIP (chromatin immunoprecipitation) is widely used for studying histone modification. Several DNA methylation-based biomarkers in context to cancer detection have been screened and purposed for its clinical utilization. Since purposed biomarkers are only proof of concept, however, their further validation in prospective studies on a larger sample subset still remains.