Neonatal necrotizing enterocolitis-associated DNA methylation signatures in the colon are evident in stool samples of affected individuals

Author:

Good Misty1ORCID,Chu Tianjiao23ORCID,Shaw Patricia3,Nolan Lila S1ORCID,McClain Lora4,Chamberlain Austin3,Castro Carlos3ORCID,Gong Qingqing1,Cooksey Krista1ORCID,Linneman Laura1,DeWitt Olivia N1,Finegold David N5ORCID,Peters David G2543ORCID

Affiliation:

1. Department of Pediatrics, Division of Newborn Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA

2. Departments of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA

3. Magee-Women’s Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA

4. Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA

5. Human Genetics, University of Pittsburgh, Pittsburgh, PA 15261, USA

Abstract

Aim: Neonatal necrotizing enterocolitis (NEC) is a deadly and unpredictable gastrointestinal disease, for which no biomarker exists. We aimed to describe the methylation patterns in stool and colon from infants with NEC. Methods: We performed a high-resolution genome-wide epigenomic analysis using solution-phase hybridization and next-generation sequencing of bisulfite-converted DNA. Results: Our data reveal significant genomic hypermethylation in NEC tissues compared with non-NEC controls. These changes were more pronounced in regions outside CpG islands and gene regulatory elements, suggesting that NEC-specific hypermethylation is not a nonspecific global phenomenon. Conclusions: This study provides evidence of a methylomic signature associated with NEC that is detectable noninvasively and provides a new opportunity for the development of a novel diagnostic method for NEC.

Funder

Children's Discovery Institute

Magee-Womens Research Institute

March of Dimes Foundation

National Institutes of Health

Pittsburgh Health Data Alliance

St. Louis Children's Hospital Foundation

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

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