Genome-wide Analysis of Aberrant DNA Methylation for Identification of Potential Biomarkers in Colorectal Cancer Patients

Background: Colorectal cancer is one of the leading causes of mortality worldwide. Genome wide analysisstudies have identified sequence mutations causing loss-of-function that are associated with disease occurrence andseverity. Epigenetic modifications, such DNA methylation, have also been implicated in many cancers but haveyet to be examined in the East Asian population of colorectal cancer patients.
Methods: Biopsies of tumors andmatched non-cancerous tissue types were obtained and genomic DNA was isolated and subjected to the bisulphiteconversion method for comparative DNA methylation analysis on the Illumina Infinium HumanMethylation27BeadChip.
Results: Totals of 258 and 74 genes were found to be hyper- and hypo-methylated as compared tothe individual’s matched control tissue. Interestingly, three genes that exhibited hypermethylation in theirpromoter regions, CMTM2, ECRG4, and SH3GL3, were shown to be significantly associated with colorectalcancer in previous studies. Using heatmap cluster analysis, eight hypermethylated and 10 hypomethylated geneswere identified as significantly differentially methylated genes in the tumour tissues.
Conclusions: Genome-widemethylation profiling facilitates rapid and simultaneous analysis of cancerous cells which may help to identifymethylation markers with high sensitivity and specificity for diagnosis and prognosis. Our results show thepromise of the microarray technology in identification of potential methylation biomarkers for colorectal cancers.