DNA methylation assay for colorectal carcinoma

Ji-Jun Chen, Ai-Qin Wang, Qing-Qi Chen

Abstract


Colorectal carcinoma (CRC) is a common cause of morbidity and mortality worldwide. Two pathogenic pathways are involved inthe development of adenoma to CRC. The first pathway involves APC/β-catenin characterized by chromosomal instabilityresulting in the accumulation of mutations. The second pathway is characterized by lesions in DNA mismatch repair genes.Aberrant DNA methylation in selected gene promoters has emerged as a new epigenetic pathway in CRC development. CRCscreening is the most efficient strategy to reduce death. Specific DNA methylation events occur in multistep carcinogenesis.Epigenetic gene silencing is a causative factor of CRC development. DNA methylations have been extensively examined in stoolfrom CRC and precursor lesions. Many methylated genes have been described in CRC and adenoma, although no definite DNAmethylation biomarkers panel has been established. Multiple DNA methylation biomarkers, including secreted frizzled-relatedprotein 2, secreted frizzled-related protein 1, tissue factor pathway inhibitor 2, vimentin, and methylguanine DNAmethyltransferase, have been further investigated, and observations have revealed that DNA methylation biomarkers exhibit withhigh sensitivity and specificity. These markers may also be used to diagnose CRC and adenoma in early stages. Real timepolymerase chain reaction (qPCR) is sensitive, scalable, specific, reliable, time saving, and cost effective. Stool exfoliated markersprovide advantages, including sensitivity and specificity. A stool qPCR methylation test may also be an enhanced tool for CRC andadenoma screening.

Keywords


Biomarker; colorectal carcinoma; DNA methylation; real time PCR; stool

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