Genome-scale DNA methylation analysis for blood-based colorectal cancer detection

Aberrant DNA hypermethylation of CpG islands occurs frequently throughout the genome in human colorectal cancer (CRC). A genome-scale DNA hypermethylation analysis technique using plasma is attractive for the noninvasive early detection of CRC. The methylated CpG tandems amplification and sequencing (MCTA-Seq) method was applied to plasma samples from 147 CRC patients and 134 controls in which 5 from the CRC patients and 2 from the control subjects failed to pass a quality control value and were excluded from further analysis. The capacity of the method for discriminating CRC and hepatocellular carcinoma (HCC) was assessed. We identified many DNA methylation markers including known (e.g., SEPT9 and IKZF1) and novel (e.g., EMBP1, KCNQ5 and CHST11) CpG islands for detecting CRC in blood. A panel of 80 markers significantly discriminated early stage CRC and controls with a sensitivity of 78% and a specificity of 90%. This method can efficiently distinguish between early stage CRC and HCC. MCTA-Seq is a promising method for the noninvasive detection of CRC that also shows great potential for identifying the tissue of origin of cancer. Overall design: The methylated CpG tandems amplification and sequencing (MCTA-Seq) method was applied to 33 tumor tissues, 33 adjacent tumor tissues and plasma samples from 147 CRC patients and 134 controls in which 5 from the CRC patients and 2 from the control subjects failed to pass a quality control value and were excluded from further analysis.