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IBD DNA Methylation

Joel Pekow, Kyle Hernandez, Katherine Meckel, Zifeng Deng, Haider I Haider, Abdurahman Khalil, Chunling Zhang, Nitya Talisila, Shivi Siva, Farzana Jasmine, Yan Chun Li, David T Rubin, Neil Hyman, Marc Bissonnette, Christopher Weber, Muhammad G Kibriya
Background and Aims: As ulcerative colitis (UC)-associated colorectal cancer (CRC) and sporadic CRC differ in presentation and molecular features, we sought to evaluate differences in the impact of DNA methylation on gene expression. Methods : NA methylation was assessed in 11 UC-CRCs and adjacent tissue and 11 sporadic CRCs and adjacent tissue using Illumina arrays. RNA sequencing was performed on 10 UC-CRCs and adjacent tissue and 8 sporadic CRCs and adjacent tissues...
February 11, 2019: Journal of Crohn's & Colitis
Hirofumi Chiba, Yoichi Kakuta, Yoshitaka Kinouchi, Yosuke Kawai, Kazuhiro Watanabe, Munenori Nagao, Takeo Naito, Motoyuki Onodera, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Kenichi Negoro, Masao Nagasaki, Michiaki Unno, Tooru Shimosegawa
[This corrects the article DOI: 10.1371/journal.pone.0194036.].
2019: PloS One
Leif Karlsson, Michela Barbaro, Ewoud Ewing, David Gomez-Cabrero, Svetlana Lajic
Prenatal treatment with dexamethasone (DEX) reduces virilization in girls with congenital adrenal hyperplasia (CAH). It has potential short- and long-term risks and has been shown to affect cognitive functions. Here, we investigate whether epigenetic modification of DNA during early developmental stages may be a key mediating mechanism by which prenatal DEX treatment could result in poor outcomes in the offspring. We analyzed genome-wide CD4+ T cell DNA methylation, assessed using the Infinium HumanMethylation450 BeadChip array in 29 individuals (mean age = 16...
January 1, 2019: Journal of the Endocrine Society
Peter M Neary, David M Schwartzberg, Turgot Bora Cengiz, Matthew F Kalady, James M Church
BACKGROUND: Sessile serrated adenomas/polyps are potentially premalignant colorectal lesions that are precursors to colorectal cancer arising via CpG island methylator phenotype. They are caused by the combination of a BRAF mutation and promoter hypermethylation. DNA methylation is an age-dependent phenomenon in the right colon, and we would expect the occurrence and severity of serrated neoplasia to reflect this. OBJECTIVE: The purpose of this study was to document the natural history of sessile serrated adenomas/polyps, including the ages at which they appear and the ranges of their number, size, and associated lesions...
December 2018: Diseases of the Colon and Rectum
Hagar Taman, Christopher G Fenton, Inga V Hensel, Endre Anderssen, Jon Florholmen, Ruth H Paulssen
Background and Aims: The aim of this study was to investigate the genome-wide DNA methylation status in treatment-naïve ulcerative colitis [UC], and to explore the relationship between DNA methylation patterns and gene expression levels in tissue biopsies from a well-stratified treatment-naïve UC patient group. Methods: Mucosal biopsies from treatment-naïve patients [n = 10], and a healthy control group [n = 11] underwent genome-wide DNA bisulfite sequencing...
November 15, 2018: Journal of Crohn's & Colitis
Daniel Azuara, Susanna Aussó, Francisco Rodriguez-Moranta, Jordi Guardiola, Xavier Sanjuan, Triana Lobaton, Jaume Boadas, Marta Piqueras, David Monfort, Elisabet Guinó, Victor Moreno, Gabriel Capellá, Javier de Oca
Background: The risk of developing colorectal cancer (CRC) is increased in patients with inflammatory bowel disease (IBD) of the colon. The aim of the study was to evaluate the effectiveness of selected methylation gene panel for the early detection of CRC in high-risk IBD patients. Methods: In a discovery phase, 73 biopsies of 48 IBD patients (associated or not to CRC) were analyzed from genome-wide DNA methylation analysis using the Illumina Human Methylation 450K BeadChip...
November 29, 2018: Inflammatory Bowel Diseases
Marta Starczak, Ewelina Zarakowska, Martyna Modrzejewska, Tomasz Dziaman, Anna Szpila, Kinga Linowiecka, Jolanta Guz, Justyna Szpotan, Maciej Gawronski, Anna Labejszo, Ariel Liebert, Zbigniew Banaszkiewicz, Maria Klopocka, Marek Foksinski, Daniel Gackowski, Ryszard Olinski
BACKGROUND: A characteristic feature of malignant cells, such as colorectal cancer cells, is a profound decrease in the level of 5-hydroxymethylcytosine, a product of 5-methylcytosine oxidation by TET enzymes. Recent studies showed that ascorbate may upregulate the activity of TET enzymes in cultured cells and enhance formation of their products in genomic DNA. METHODS: The study included four groups of subjects: healthy controls (n = 79), patients with inflammatory bowel disease (IBD, n = 51), adenomatous polyps (n = 67) and colorectal cancer (n = 136)...
July 20, 2018: Journal of Translational Medicine
Tomasz Dziaman, Daniel Gackowski, Jolanta Guz, Kinga Linowiecka, Magdalena Bodnar, Marta Starczak, Ewelina Zarakowska, Martyna Modrzejewska, Anna Szpila, Justyna Szpotan, Maciej Gawronski, Anna Labejszo, Ariel Liebert, Zbigniew Banaszkiewicz, Maria Klopocka, Marek Foksinski, Andrzej Marszalek, Ryszard Olinski
Background: Active demethylation of 5-methyl-2'-deoxycytidine (5-mdC) in DNA occurs by oxidation to 5-(hydroxymethyl)-2'-deoxycytidine (5-hmdC) and further oxidation to 5-formyl-2'-deoxycytidine (5-fdC) and 5-carboxy-2'-deoxycytidine (5-cadC), and is carried out by enzymes of the ten-eleven translocation family (TETs 1, 2, 3). Decreased level of epigenetic DNA modifications in cancer tissue may be a consequence of reduced activity/expression of TET proteins. To determine the role of epigenetic DNA modifications in colon cancer development, we analyzed their levels in normal colon and various colonic pathologies...
2018: Clinical Epigenetics
John B Kisiel, Pasquale Klepp, Hatim T Allawi, William R Taylor, Maria Giakoumopoulos, Tamara Sander, Tracy C Yab, Bjorn A Moum, Graham P Lidgard, Stephan Brackmann, Douglas W Mahoney, Arne Roseth, David A Ahlquist
BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are at increased risk for colorectal cancer (CRC). Analyses of DNA methylation patterns in stool samples have been reported to detect CRC in patients with IBD. We sought to validate these findings in larger cohorts and assess the accuracy of analysis of DNA methylation patterns in stool for detection of CRC and high-grade dysplasia (HGD) normalized to methylation level at ZDHHC1...
May 15, 2018: Clinical Gastroenterology and Hepatology
Hirofumi Chiba, Yoichi Kakuta, Yoshitaka Kinouchi, Yosuke Kawai, Kazuhiro Watanabe, Munenori Nagao, Takeo Naito, Motoyuki Onodera, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Kenichi Negoro, Masao Nagasaki, Michiaki Unno, Tooru Shimosegawa
BACKGROUND: Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs...
2018: PloS One
Adrian Frick, Vineeta Khare, Gregor Paul, Michaela Lang, Franziska Ferk, Siegfried Knasmüller, Andrea Beer, Georg Oberhuber, Christoph Gasche
Patients with inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated-cancer (CAC); however, the underlying processes of disease progression are not completely understood. Here, the molecular processes of inflammation-driven colon carcinogenesis were investigated using IL10-deficient mice (IL10 KO). IL10 KO mice were euthanized after development of colitis and dysplasia. IHC was performed for markers of colitis-induced DNA damage (CIDD): oxidative DNA lesions (8-oxoG), double-strand breaks (DSB; γH2AX)...
April 2018: Molecular Cancer Research: MCR
Pasquale Klepp, John B Kisiel, Milada Cvancarova Småstuen, Arne Røseth, Solveig N Andersen, Morten H Vatn, David A Ahlquist, Bjørn A Moum, Stephan Brackmann
BACKGROUND AND AIM: Colonoscopic surveillance is recommended in patients with longstanding inflammatory bowel disease (IBD) as they are at increased risk of colorectal cancer (CRC). Non-invasive surveillance may improve compliance and access. Multi-target stool DNA (MT-sDNA) has been validated for screening of sporadic CRC but has not been assessed in IBD. Our aim was to assess the performance of a MT-sDNA test in a real-life surveillance setting of patients with longstanding IBD. MATERIAL AND METHODS: A total of 192 IBD patients enrolled from two prospective cohorts submitted an EDTA buffered stool sample and underwent chromo- or white light colonoscopy...
March 2018: Scandinavian Journal of Gastroenterology
Anoop Kumar, Pooja Malhotra, Hayley Coffing, Shubha Priyamvada, Arivarasu N Anbazhagan, Harish R Krishnan, Ravinder K Gill, Waddah A Alrefai, David P Gavin, Subhash C Pandey, Pradeep K Dudeja, Seema Saksena
Na+ /H+ exchanger-3 (NHE3) is crucial for intestinal Na+ absorption, and its reduction has been implicated in infectious and inflammatory bowel diseases (IBD)-associated diarrhea. Epigenetic mechanisms such as DNA methylation are involved in the pathophysiology of IBD. Whether changes in DNA methylation are involved in modulating intestinal NHE3 gene expression is not known. Caco-2 and HuTu 80 cells were used as models of human intestinal epithelial cells. Normal C57/BL6, wild-type, or growth arrest and DNA damage-inducible 45b (GADD45b) knockout (KO) mice were used as in vivo models...
March 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Kate Joanne Howell, Judith Kraiczy, Komal M Nayak, Marco Gasparetto, Alexander Ross, Claire Lee, Tim N Mak, Bon-Kyoung Koo, Nitin Kumar, Trevor Lawley, Anupam Sinha, Philip Rosenstiel, Robert Heuschkel, Oliver Stegle, Matthias Zilbauer
BACKGROUND & AIMS: We analyzed DNA methylation patterns and transcriptomes of primary intestinal epithelial cells (IEC) of children newly diagnosed with inflammatory bowel diseases (IBD) to learn more about pathogenesis. METHODS: We obtained mucosal biopsies (N = 236) collected from terminal ileum and ascending and sigmoid colons of children (median age 13 years) newly diagnosed with IBD (43 with Crohn's disease [CD], 23 with ulcerative colitis [UC]), and 30 children without IBD (controls)...
February 2018: Gastroenterology
Yahui Zhu, Li Gu, Yajun Li, Xi Lin, Hongxing Shen, Kaisa Cui, Li Chen, Feng Zhou, Qiu Zhao, Jinxiang Zhang, Bo Zhong, Edward Prochownik, Youjun Li
miR-148a has been shown to regulate inflammation, immunity and the growth of certain tumors, but its roles in colitis and colorectal tumorigenesis remain largely undetermined. Here we found miR-148a-deficient mice to be more susceptible to colitis and colitis-associated tumorigenesis. Both were associated with increased nuclear factor κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) signaling. Bone marrow- and non-bone marrow-derived miR-148a contributed to colitis and colitis-associated tumorigenesis...
December 2017: Cell Death and Differentiation
Ming Zhang, Lixing Zhou, Shu Zhang, Yang Yang, Lei Xu, Zichun Hua, Xiaoping Zou
Bifidobacterium longum (B. Longum) is a common probiotic colonized in the human gut and against the development of chronic inflammation including inflammatory bowel disease (IBD). But the underlying mechanism remains unknown. The aim of this study was to evaluate the affection of B. longum on the methylation levels of forkhead box P3 (Foxp3) promoter. 2, 4, 6-trinitrobenzenesulphonic acid (TNBS)-induced colitis rat models were treated with B. longum or medium, respectively. The genomic DNA of spleen peripheral blood mononuclear cells (PBMC) cells was extracted...
September 2017: Microbial Pathogenesis
Rivkah Gonsky, Phillip Fleshner, Richard L Deem, Eva Biener-Ramanujan, Dalin Li, Alka A Potdar, Janine Bilsborough, Shaohong Yang, Dermot P B McGovern, Stephan R Targan
BACKGROUND & AIMS: Variants in the tumor necrosis factor superfamily member 15 gene (TNFSF15, also called TL1A) have been associated with risk for inflammatory bowel disease (IBD). TL1A affects expression of multiple cytokines to promote mucosal inflammation. Little is known about the TL1A-response pathways that regulate cytokine expression. We investigated T-cell gene expression patterns to determine the mechanisms by which TL1A regulates cytokine production, and whether these associate with outcomes of patients with Crohn's disease (CD)...
July 2017: Gastroenterology
Bobak Parang, Andrew M Kaz, Caitlyn W Barrett, Sarah P Short, Wei Ning, Cody E Keating, Mukul K Mittal, Rishi D Naik, Mary K Washington, Frank L Revetta, J Joshua Smith, Xi Chen, Keith T Wilson, Thomas Brand, David M Bader, William P Tansey, Ru Chen, Teresa A Brentnall, William M Grady, Christopher S Williams
OBJECTIVE: Blood vessel epicardial substance (BVES) is a tight junction-associated protein that regulates epithelial-mesenchymal states and is underexpressed in epithelial malignancy. However, the functional impact of BVES loss on tumourigenesis is unknown. Here we define the in vivo role of BVES in colitis-associated cancer (CAC), its cellular function and its relevance to patients with IBD. DESIGN: We determined BVES promoter methylation status using an Infinium HumanMethylation450 array screen of patients with UC with and without CAC...
May 2017: Gut
Matthias Zilbauer, Judith Kraiczy
Epigenetics can be defined as stable, potentially heritable changes in cellular phenotype caused by mechanisms other than alterations in the underlying DNA sequence. DNA methylation is amongst the most intensely studied epigenetic mechanisms and has been shown to play a major role in regulating fundamental aspects of cell biology including cellular differentiation, organ development, and cell type-specific gene expression. Importantly, it is becoming increasingly clear that epigenetic mechanisms operate at the interface between the genetic code and our environment and are able to mediate environmental changes into stable phenotypic alterations...
2017: Nestlé Nutrition Institute Workshop Series
Deborah Saraggi, Matteo Fassan, Claudia Mescoli, Marco Scarpa, Nicola Valeri, Andrea Michielan, Renata D'Incá, Massimo Rugge
In spite of the well-established histopathological phenotyping of IBD-associated preneoplastic and neoplastic lesions, their molecular landscape remains to be fully elucidated. Several studies have pinpointed the initiating role of longstanding/relapsing inflammatory insult on the intestinal mucosa, with the activation of different pro-inflammatory cytokines (TNF-α, IL-6, IL-10, IFN-γ), chemokines and metabolites of arachidonic acid resulting in the activation of key transcription factors such as NF-κB. Longstanding inflammation may also modify the intestinal microbiota, prompting the overgrowth of genotoxic microorganisms, which may act as further cancer promoters...
April 2017: Digestive and Liver Disease
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