Potential Link Between Fusobacterium Enrichment and DNA Methylation Accumulation in the Inflammatory Colonic Mucosa in Ulcerative Colitis

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Oct 6

PMID 28977914

Citations 31

Authors

Tomomitsu Tahara

Ichiro Hirata

Naoko Nakano

Sayumi Tahara

Noriyuki Horiguchi

Tomohiko Kawamura

Masaaki Okubo

Takamitsu Ishizuka

Hyuga Yamada

Dai Yoshida

Takafumi Ohmori

Kohei Maeda

Naruomi Komura

Hirokazu Ikuno

Yasutaka Jodai

Toshiaki Kamano

Mitsuo Nagasaka

Yoshihito Nakagawa

Tetsuya Tuskamoto

Makoto Urano

Tomoyuki Shibata

Makoto Kuroda

Naoki Ohmiya

Affiliations

Soon will be listed here.

Abstract

Background And Aim: enrichment has been associated with colorectal cancer development. Ulcerative colitis (UC) associated tumorigenesis is characterized as high degree of methylation accumulation through continuous colonic inflammation. The aim of this study was to investigate a potential link between enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in UC.

Methods: In the candidate analysis, inflamed colonic mucosa from 86 UC patients were characterized the methylation status of colorectal a panel of cancer related 24 genes. In the genome-wide analysis, an Infinium HumanMethylation450 BeadChip array was utilized to characterize the methylation status of >450,000 CpG sites for fourteen UC patients. Results were correlated with status.

Results: UC with enrichment (FB-high) was characterized as high degree of type C (for cancer-specific) methylation compared to other (FB-low/neg) samples (<0.01). Genes hypermethylated in FB-high samples included well-known type C genes in colorectal cancer, such as and , and . Multivariate analysis demonstrated that the FB high status held an increased likelihood for methylation high as an independent factor (odds ratio: 16.18, 95% confidence interval: 1.94-135.2, =0.01). Genome-wide methylation analysis demonstrated a unique methylome signature of FB-high cases irrespective of promoter, outside promoter, CpG and non-CpG sites. Group of promoter CpG sites that were exclusively hypermethylated in FB-high cases significantly codified the genes related to the catalytic activity (=0.039).

Conclusion: Our findings suggest that accelerates DNA methylation in specific groups of genes in the inflammatory colonic mucosa in UC.

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