Epigenome-Wide Study Identifies Epigenetic Outliers in Normal Mucosa of Patients with Colorectal Cancer.

Autor:	Ghosh J; Fels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania., Schultz BM; Fels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania., Chan J; Fels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania., Wultsch C; Bioinformatics and Computational Genomics Laboratory, Hunter College, City University of New York, New York, New York.; Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, New York., Singh R; Bioinformatics and Computational Genomics Laboratory, Hunter College, City University of New York, New York, New York., Shureiqi I; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan., Chow S; Nutrition Department, School of Urban Public Health at Hunter College, New York, New York., Doymaz A; Department of Chemistry, Hunter College, City University of New York, New York, New York., Varriano S; The Graduate Center, City University of New York, New York, New York., Driscoll M; Northwell Health Imbert Cancer Center, Bayshore, New York., Muse J; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York., Kleiman FE; Department of Chemistry, Hunter College, City University of New York, New York, New York., Krampis K; Bioinformatics and Computational Genomics Laboratory, Hunter College, City University of New York, New York, New York.; Department of Biological Sciences, Hunter College, City University of New York, New York, New York.; Institute of Computational Biomedicine, Weill Cornell Medical College, New York, New York., Issa JJ; Coriell Institute for Medical Research, Camden, New Jersey., Sapienza C; Fels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.
Jazyk:	angličtina
Zdroj:	Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2022 Nov 01; Vol. 15 (11), pp. 755-766.
DOI:	10.1158/1940-6207.CAPR-22-0258
Abstrakt:	Nongenetic predisposition to colorectal cancer continues to be difficult to measure precisely, hampering efforts in targeted prevention and screening. Epigenetic changes in the normal mucosa of patients with colorectal cancer can serve as a tool in predicting colorectal cancer outcomes. We identified epigenetic changes affecting the normal mucosa of patients with colorectal cancer. DNA methylation profiling on normal colon mucosa from 77 patients with colorectal cancer and 68 controls identified a distinct subgroup of normally-appearing mucosa with markedly disrupted DNA methylation at a large number of CpGs, termed as "Outlier Methylation Phenotype" (OMP) and are present in 15 of 77 patients with cancer versus 0 of 68 controls (P < 0.001). Similar findings were also seen in publicly available datasets. Comparison of normal colon mucosa transcription profiles of patients with OMP cancer with those of patients with non-OMP cancer indicates genes whose promoters are hypermethylated in the OMP patients are also transcriptionally downregulated, and that many of the genes most affected are involved in interactions between epithelial cells, the mucus layer, and the microbiome. Analysis of 16S rRNA profiles suggests that normal colon mucosa of OMPs are enriched in bacterial genera associated with colorectal cancer risk, advanced tumor stage, chronic intestinal inflammation, malignant transformation, nosocomial infections, and KRAS mutations. In conclusion, our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Prospective studies are needed to determine whether OMP could serve as a biomarker for an elevated epigenetic risk for colorectal cancer development. Prevention Relevance: Our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Identification of OMPs in healthy controls and patients with colorectal cancer will lead to prevention and better prognosis, respectively. (©2022 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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