Methylated-CpG island recovery assay-assisted microarrays for cancer diagnosis

Alterations in DNA methylation patterns occur in every type of human cancer and are considered a hallmark of malignant transformation. Most notable is the cancer-associated hypermethylation of CpG-rich sequences, the so-called CpG islands, which are often found near the 5' ends and promoters of genes. This CpG island methylation represents a positive signal that can be used to distinguish malignant tissue from normal tissue. Thus, characterization of CpG island hypermethylation has become a valuable tool for cancer detection and diagnosis. There are several methods used for detection of gene-specific DNA methylation. However, besides looking at individual genes, an even greater potential lies in the characterization of genome-wide changes of DNA methylation patterns in tumors. The authors propose that tumor type- and tumor subtype-specific DNA methylation patterns exist and can be exploited for the classification of cancers, their response to therapy and their metastatic potential, and thus may have predictive value. Various methods for genome-wide analysis of DNA methylation have been developed. These methods are described briefly and the methylated-CpG island recovery assay will be reviewed. This assay has been used in combination with microarray analysis to map CpG island methylation across cancer genomes.