The development of CpG island methylation biomarkers using restriction landmark genomic scanning

CpG island hypermethylation is a common occurrence in cancer. Because this is a stable molecular alteration of the DNA, which can be detected easily from very small amounts, DNA methylation is an attractive candidate to use as a molecular biomarker. Recent studies have used DNA methylation of genes known to be targets of genetic disruption in cancer as biomarkers for early detection of cancer, classification of malignancies, response to drug treatment, and as markers predictive of outcome. Since many of the currently used targets of methylation are methylated at rather low frequencies in various cancer types even though the gene may be frequently disrupted by other mechanisms, it would be useful to develop additional markers that are methylated at high frequency in the cancer being studied. Restriction landmark genomic scanning has been used for the identification of frequent targets of methylation in multiple malignancies. These markers, which can be either cancer type-specific or nonspecific, may prove to be effective biomarkers for diagnostic or prognostic purposes, or for midpoint analysis of intervention strategies.