Abstract
patients with stage II, microsatellite stable colon cancer with clinical data and of colon mucosa samples from 50 healthy donors, obtained during routine colonoscopy using the newly developed 450,000 CpG site platform for DNA methylation studies (Illumina Infinium HumanMethylation450BeadChip). This array includes CpG and CNG sites, CpG islands/shores/shelves/isolated CpGs in the genome, non-coding RNA (microRNAs and long non-coding RNAs) and sites surrounding the transcription start sites (−200 bp to −1,500 bp, 5′-UTRs and exons 1) for coding genes, but also for the corresponding gene bodies and 3′-UTRs. This study has been developed in the context of the COLONOMICS project (www.colonomics.org) in which for those normal-tumor paired samples and controls we also have data on molecular expression, SNPs/CNVs and miRNAs. The biomarkers identified must be validated. Results and Discussion: The preliminary analysis of the methylation patterns among different groups show differences in the methylation patterns of tumor and normal mucosa. A total of 106,566 CpG sites were differentially methylated between tumor and normal tissue (at 5% significance level after Bonferroni correction). The analyses of principal component (PCA) clearly discriminate between tumor and normal tissue samples. Some tumors show a predominant tumor hypermethylation pattern while others show hypomethylation and these patterns depict tumor subgroups that are likely to have different phenotype and outcomes. Epigenetic events may contain prognostic information. Using supervised analyses we have been able to identify several potential candidates for diagnostic and prognostic biomarkers to discriminate between tumor and non-tumor tissues. Conclusion: These differences in the methylation patterns shown to be promising in predicting the diagnostic and prognosis of CRC patients based on epigenetic characteristics of the tumors and normal mucosa.
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