Epigenetic diagnostics of cancer — the application of DNA methylation markers

Abstract

In recent years it has become apparent that epigenetic events are potentially equally responsible for cancer initiation and progression as genetic abnormalities. DNA methylation is the main epigenetic modification in humans. Two DNA methylation lesions coexist in human neoplasms: hypermethylation of promoter regions of specific genes within a context of genomic hypomethylation. Aberrant methylation is found at early stages of carcinogenesis and distinct types of cancer exhibit specific patterns of methylation changes. Tumor specific DNA is readily obtainable from different clinical samples and methylation status analysis often permits sensitive disease detection. Methylation markers may also serve for prognostic and predictive purposes as they often reflect the metastatic potential and sensitivity to therapy. As current findings show a great potential of recently characterised methylation markers, more studies in the field are needed in the future. Large clinical studies of newly developed markers are especially needed. The review describes the diagnostic potential of DNA methylation markers.

Frequency variations in the methylated pattern of p73/p21 genes and chromosomal aberrations correlating with different grades of glioma among south Indian population

“…Characterizing the detected tumor is another necessary step in the course of therapy. Methylation markers may serve for both of these goals [16]. Methylation profiling of the promoter CpG islands, chromosomal aberrations, and the effect of DNA methylation at the gene expression level have been an important information gathering process for new insights in understanding of the role of DNA methylation in both initiation and progression in cancer [17].…”

“…Based on the observation, it will be beneficial to stratify patients by methylation status in future clinical trials in GBM, and possible to assign alternate treatments to patients with high levels of methylation. Ultimately, patients with high levels of methylation may be best treated by drugs that affect epigenetic processes [16], perhaps to be followed by standard chemotherapy approaches. Our findings are the first to document a poorer prognostic impact of methylation (76.2%) in different grades of glioma in south Indian population in a multivariate analysis.…”

A Proof-of-Principle Demonstration of a Novel Microarray-Based Method for Quantifying DNA Methylation Levels

“…It alters gene expression pattern stably and forms the basis of chromatin structure, and changes in DNA methylation prior to gene expression [5,6]. Methylation associated with transcriptional regulation generally occurs on CpG islands located in the promoter, and first exon of genes [7].…”

Clinicopathological Significance of BRCA1 Promoter Hypermethylation in Thai Breast Cancer Patients

“…In the emerging epigenetic field, hypermethylation of CpG islands in the gene promoter region is an important mechanism leading to changes in gene expression, without altering genetic code (Paluszczak et al, 2006). This study aimed to investigate the role of the BRCA1 hypermethylation epigenetic mechanism in Thai breast-cancer patients, to clarify the relevant prognostic biomarkers for breast cancer.…”