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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Distinct patterns of DNA methylation in conventional adenomas involving the right and left colon.

Authors: Koestler, Devin C; Li, Jing; Baron, John A; Tsongalis, Gregory J; Butterly, Lynn F; Goodrich, Martha; Lesseur, Corina; Karagas, Margaret R; Marsit, Carmen J; Moore, Jason H; Andrew, Angeline S; Srivastava, Amitabh

Published In Mod Pathol, (2014 Jan)

Abstract: Recent studies have shown two distinct non-CIMP methylation clusters in colorectal cancer, raising the possibility that DNA methylation, involving non-CIMP genes, may play a role in the conventional adenoma-carcinoma pathway. A total of 135 adenomas (65 left colon and 70 right colon) were profiled for epigenome-wide DNA methylation using the Illumina HumanMethylation450 BeadChip. A principal components analysis was performed to examine the association between variability in DNA methylation and adenoma location. Linear regression and linear mixed effects models were used to identify locus-specific differential DNA methylation in adenomas of right and left colon. A significant association was present between the first principal component and adenoma location (P=0.007), even after adjustment for subject age and gender (P=0.009). A total of 168 CpG sites were differentially methylated between right- and left-colon adenomas and these loci demonstrated enrichment of homeobox genes (P=3.0 × 10(-12)). None of the 168 probes were associated with CIMP genes. Among CpG loci with the largest difference in methylation between right- and left-colon adenomas, probes associated with PRAC (prostate cancer susceptibility candidate) gene showed hypermethylation in right-colon adenomas whereas those associated with CDX2 (caudal type homeobox transcription factor 2) showed hypermethylation in left-colon adenomas. A subgroup of left-colon adenomas enriched for current smokers (OR=6.1, P=0.004) exhibited a methylation profile similar to right-colon adenomas. In summary, our results indicate distinct patterns of DNA methylation, independent of CIMP genes, in adenomas of the right and left colon.

PubMed ID: 23868178 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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