COMPARE-MS: a Novel Technique for Rapid, Sensitive, and Accurate Detection of DNA Methylation
Hypermethylation of CpG island (CGI) sequences is a nearly universal somatic genome alteration in cancer. The rapid and sensitive detection of DNA hypermethylation can aid in cancer diagnosis and risk stratification but its detection has remained labor-intensive and time-consuming. To address these issues, scientists at JHU developed a novel technology, called COMPARE-MS (Combination of Methylated-DNA Precipitation and Methylation Sensitive Restriction Enzymes), that can rapidly and quantitatively detect CGI hypermethylation with exquisite sensitivity and specificity in hundreds of samples simultaneously, without subjecting DNA samples to sodium bisulfite conversion. In a validation study, the inventors demonstrated that COMPARE-MS could differentiate between malignant and benign prostate tissues with tremendous sensitivity (~95%) and specificity (-100%). Description (Set) Proposed Use (Set) This novel technology has significant advantages over existing DNA methylation detection strategies. First, it does not require sodium-bisulfite treatment and therefore avoids the pitfalls associated with bisulfite conversion. Instead, COMPARE-MS uses a novel strategy that combines methylation-sensitive restriction enzyme digestion with capture of methylated DNA by methyl-binding domain polypeptides to highly enrich for methylated DNA. COMPARE-MS is also highly amenable to automated, high-throughput, micro-titer plate platforms. This technology can be used as a research tool for epigenetic marker identification in specific cancer types, in addition to its use as a screening tool for determining cancer susceptibility and diagnosis.
Nelson, William G.
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