Quantitative assessment of DNA methylation: potential applications for disease diagnosis, classification, and prognosis in clinical settings

Abstract

Deregulation of the epigenome is now recognized as a major mechanism involved in the development and progression of human diseases such as cancer. As opposed to the irreversible nature of genetic events, which introduce changes in the primary DNA sequence, epigenetic modifications are reversible and leave the original DNA sequence intact. There is now evidence that the epigenetic landscape in humans undergoes modifications as the result of normal aging, with older individuals exhibiting higher levels of promoter hypermethylation compared to younger ones. Thus, it has been proposed that the higher incidence of certain disease in older individuals might be, in part, a consequence of an inherent change in the control and regulation of the epigenome. These observations are of remarkable clinical significance since the aberrant epigenetic changes characteristic of disease provide a unique platform for the development of new therapeutic approaches. In this review, we address the significance of DNA methylation changes that result or lead to disease, occur with aging, or may be the result of environmental exposure. We provide a detailed description of quantitative techniques currently available for the detection and analysis of DNA methylation and provide a comprehensive framework that may allow for the incorporation of protocols which include DNA methylation as a tool for disease diagnosis and classification, which could lead to the tailoring of therapeutic approaches designed to individual patient needs.

Potential utility of HOP homeobox gene promoter methylation as a marker of tumor aggressiveness in gastric cancer

“…The algorithm development to circumvent the subjective and equivocal interpretation of HOPX expression status including optimal protocols of tissue fixation and staining procedure were required to finally conclude the comparison of the methodologies. On the other hand, Q-MSP can achieve much more objective and specific assessment in a small amount of genomic DNA through PCR amplification using methylation-specific primers and fluorescent probe (Brena et al, 2006). For these reasons, at present, we believe that quantitative assessment of HOPX-b methylation is the preferable method for tumor aggressiveness marker of advanced gastric cancer.…”

Array-Based Multiplex Analysis of DNA Methylation in Breast Cancer Tissues

“…22,23 Unfortunately there is only a limited probability of methylation for each gene, 24 so only a combined measurement of multiple methylation biomarkers may provide useful data. The M 3 -assay is developed to generate such composite biomarkers.…”

Promoter methylation negatively correlated with mRNA expression but not tissue differential expression after heat stress

“…Aberrant DNA methylation is associated with gene silencing or downregulation (Bird, 2002;Dai et al, 2003). Studies of human diseases have revealed that complex diseases such as cancer are often associated with sudden hypermethylation of tumor suppressor genes or hypomethylation of cancer-related genes (Robertson and Wolffe, 2000;Brena et al, 2006). Methylation of the CpG island within the promoter prevents protein binding at DNA methylation sites, directly inhibiting gene transcription because when double-stranded DNA forms a three-dimensional structure, the methyl of methylated cytosine may be highlighted in the major groove, blocking the interaction between transcription factors and genes (Kuroda et al, 2009).…”