Evaluation of Methylation Biomarkers for Detection of Circulating Tumor DNA and Application to Colorectal Cancer
AbstractSolid tumors shed DNA into circulation, and there is growing evidence that the detection of circulating tumor DNA (ctDNA) has broad clinical utility, including monitoring of disease, prognosis, response to chemotherapy and tracking tumor heterogeneity. The appearance of ctDNA in the circulating cell-free DNA (ccfDNA) isolated from plasma or serum is commonly detected by identifying tumor-specific features such as insertions, deletions, mutations and/or aberrant methylation. Methylation is a normal cell regulatory event, and since the majority of ccfDNA is derived from white blood cells (WBC), it is important that tumour-specific DNA methylation markers show rare to no methylation events in WBC DNA. We have used a novel approach for assessment of low levels of DNA methylation in WBC DNA. DNA methylation in 29 previously identified regions (residing in 17 genes) was analyzed in WBC DNA and eight differentially-methylated regions (DMRs) were taken through to testing in clinical samples using methylation specific PCR assays. DMRs residing in four genes, BCAT1, GRASP, IKZF1 and IRF4, exhibited low positivity, 3.5% to 7%, in the plasma of colonoscopy-confirmed healthy subjects, with the sensitivity for detection of ctDNA in colonoscopy-confirmed patients with colorectal cancer being 65%, 54.5%, 67.6% and 59% respectively. View Full-Text
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Mitchell, S.M.; Ho, T.; Brown, G.S.; Baker, R.T.; Thomas, M.L.; McEvoy, A.; Xu, Z.-Z.; Ross, J.P.; Lockett, T.J.; Young, G.P.; LaPointe, L.C.; Pedersen, S.K.; Molloy, P.L. Evaluation of Methylation Biomarkers for Detection of Circulating Tumor DNA and Application to Colorectal Cancer. Genes 2016, 7, 125.
Mitchell SM, Ho T, Brown GS, Baker RT, Thomas ML, McEvoy A, Xu Z-Z, Ross JP, Lockett TJ, Young GP, LaPointe LC, Pedersen SK, Molloy PL. Evaluation of Methylation Biomarkers for Detection of Circulating Tumor DNA and Application to Colorectal Cancer. Genes. 2016; 7(12):125.Chicago/Turabian Style
Mitchell, Susan M.; Ho, Thu; Brown, Glenn S.; Baker, Rohan T.; Thomas, Melissa L.; McEvoy, Aidan; Xu, Zheng-Zhou; Ross, Jason P.; Lockett, Trevor J.; Young, Graeme P.; LaPointe, Lawrence C.; Pedersen, Susanne K.; Molloy, Peter L. 2016. "Evaluation of Methylation Biomarkers for Detection of Circulating Tumor DNA and Application to Colorectal Cancer." Genes 7, no. 12: 125.
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