Project description:Integrative Epigenome-Wide Analysis Shows That DNA Methylation May Mediate Genetic Risk In Inflammatory Bowel Disease [Cells, Methylation profiling]
Project description:Integrative Epigenome-Wide Analysis Shows That DNA Methylation May Mediate Genetic Risk In Inflammatory Bowel Disease [Whole blood, Methylation profiling]
Project description:Inflammation has long been recognized to contribute to cancer development, particularly across the gastrointestinal tract. Patients with inflammatory bowel disease have an increased risk for bowel cancers, and it has been posited that a field of genetic changes may underlie this risk. Wnt pathway alterations are infrequent, and our data suggest transcriptional rewiring away from Wnt. These findings suggest neoplastic bowel lesions developing in a background of inflammation experience lineage plasticity away from Wnt activation early during tumorigenesis and largely occur as genetically independent events.
Project description:Inflammation has long been recognized to contribute to cancer development, particularly across the gastrointestinal tract. Patients with inflammatory bowel disease have an increased risk for bowel cancers, and it has been posited that a field of genetic changes may underlie this risk. Wnt pathway alterations are infrequent, and our data suggest transcriptional rewiring away from Wnt. These findings suggest neoplastic bowel lesions developing in a background of inflammation experience lineage plasticity away from Wnt activation early during tumorigenesis and largely occur as genetically independent events.
Project description:Inflammation has long been recognized to contribute to cancer development, particularly across the gastrointestinal tract. Patients with inflammatory bowel disease have an increased risk for bowel cancers, and it has been posited that a field of genetic changes may underlie this risk. Wnt pathway alterations are infrequent, and our data suggest transcriptional rewiring away from Wnt. These findings suggest neoplastic bowel lesions developing in a background of inflammation experience lineage plasticity away from Wnt activation early during tumorigenesis and largely occur as genetically independent events.
Project description:Ulcerative colitis is heritable disorder with variable clinical outcome but to date only less than 10% of the disease susceptibility and the disease outcome is explained by IBD (inflammatory bowel disease) associated genetic loci. This missing heritability lay fertile grounds for investigating epigenetics as possible explanation. The aims of the study were to investigate genome-wide DNA methylation of the rectal tissue in an inception cohort of UC at two time points, once at baseline (treatment naïve) and at follow-up to explore how longitudinal DNA methylation influences the disease onset, disease progression and outcome. For this purpose, we profiled DNA methylation within rectal mucosal biopsies of pediatric UC (n=211) and non-IBD control patients (n=85) to perform epigenome-wide association studies (EWAS) of specific cell types (i.e epithelial, immune, and fibroblast), to identify UC specific differences. We have also performed longitudinal analysis on follow-up samples (n =73), and also additional comparisons were made between patients eventually undergoing colectomy versus those who did not.
