Identifying Clinicopathological Association of DNA Hypermethylation in Cancers Using CpG Island Microarrays

Hypermethylation of promoter CpG islands has been associated with gene silencing in cancer. Increasingly, these CpG islands have potential clinical utility as molecular markers for cancer diagnosis. Here we describe a microarray-based technique, called differential methylation hybridization (DMH), for simultaneous screening of methylation alteration across thousands of CpG island loci in one tumor sample at a time. We also describe a second approach, called methylation target array (MTA), for detecting methylation alteration of a single CpG island locus across hundreds of tumor DNA samples. The DMH and MTA assays are complementary to each other in that DMH allows for rapid identification of multiple loci hypermethylated in tumor genomes while MTA can rapidly assess the utility of these loci as markers for clinical diagnosis. Furthermore, the use of clustering algorithms to analyze the array data of multiple CpG island loci can identify an association of DNA hypermethylation with specific clinicopathological features of tumors.

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