Genome wide DNA methylation of colon low grade and high grade adenoma

ABSTRACT: Introduction: The dynamics of colorectal epigenetics during early carcinogenesis remain undocumented. In this study, we explore the DNA methylation dynamics in colorectal cancer oncogenesis from non-tumor colon tissues to low-grade, high-grade adenoma and adenocarcinoma. Methods: The methylome of 13 low-grade and 19 high-grade colorectal adenomas was determined using the EPIC v1 Human Methylation Beadchip. These methylation profiles were complemented with the methylomes of 206 non-tumor colon and 24 colon adenocarcinomas from GSE149282, GSE132804 series and the HCMI study. Differentially methylated CpG were identified by Student's t-test and used to monitor the evolution of the colon methylome during carcinogenesis. The differentially methylated promoters were used to infer the associated biological process using gene ontology. Results: 4.9% of the colon methylome is significantly altered (p < 10-4) during carcinogenesis with two thirds corresponding to DNA demethylation. 56.6% of the methylation changes occurs at the transition from non-tumor colon tissues to low-grades adenomas. 18.2% of the DNA methylation changes are transitory during low-grade and/or high-grade adenomas. The biological pathways sensory perception of odor and stimulus were early unmethylated, nervous system development and homophilic cell adhesion were early methylated, and chemical synaptic transmission and cell adhesion were transiently methylated. Conclusion: This study provides insight into the dynamics of colonic epigenetics during carcinogenesis, with early DNA methylation changes in the low-grade adenomas associated with transient DNA methylation changes. However, the causality of these changes remains to be elucidated.

ORGANISM(S): Homo sapiens

PROVIDER: GSE288652 | GEO | 2025/12/18

REPOSITORIES: GEO