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| Open AccessMulti-omic cross-sectional cohort study of pre-malignant Barrett’s esophagus reveals early structural variation and retrotransposon activity
The alterations associated with progression from Barrett’s esophagus (BE) to esophageal adenocarcinoma are not fully characterised. Here, the authors perform a multi-omics analysis of a longitudinally-sampled BE patient cohort, identifying the impact of structural variants, including mobile elements, and the timing of molecular events during progression.
- A. C. Katz-Summercorn
- , S. Jammula
- & R. C. Fitzgerald
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Article
| Open AccessDesmoplakin and periplakin genetically and functionally contribute to eosinophilic esophagitis
Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease with a complex underlying genetic etiology. Here, the authors identify a series of rare variants in DSP and PPL in multiplex families with EoE and uncover a pathogenic role for desmosomal dysfunction in EoE.
- Tetsuo Shoda
- , Kenneth M. Kaufman
- & Marc E. Rothenberg
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Article
| Open AccessGWAS of peptic ulcer disease implicates Helicobacter pylori infection, other gastrointestinal disorders and depression
Genetic factors contribute to peptic ulcer disease (PUD). Here, the authors perform a genome-wide association analysis on PUD in the UK Biobank, highlighting shared architecture with other gastrointestinal disorders and possible causal links with depression.
- Yeda Wu
- , Graham K. Murray
- & Naomi R. Wray
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Article
| Open AccessIdentification of predictors of drug sensitivity using patient-derived models of esophageal squamous cell carcinoma
Predicting the drug response of patients with cancer is crucial for implementing targeted therapy. Here, Su et al. make patient-derived cell lines and perform targeted sequencing and RNA-seq to identify CDKN2A/2B loss as a predictor of response to CDK4/6 inhibitors in esophageal squamous cell carcinoma.
- Dan Su
- , Dadong Zhang
- & Weimin Mao
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Article
| Open AccessGastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases
Gastroesophageal reflux disease (GERD) is a major risk factor for Barret’s esophagus (BE) and esophageal adenocarcinoma (EA). Here, An et al. report 25 genetic loci for GERD, many of which associate with BE and EA or with other traits such as BMI.
- Jiyuan An
- , Puya Gharahkhani
- & Stuart MacGregor
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Article
| Open AccessSingle cell RNA-seq reveals profound transcriptional similarity between Barrett’s oesophagus and oesophageal submucosal glands
Barrett’s oesophagus is associated with an increased risk of oseophageal cancer, but its cell of origin is unclear. Here the authors show, using single-cell RNA sequencing of biopsies from six patients and two unaffected subjects, that cells in Barrett’s oesophagus show a transcriptional profile that is similar to that of cells in oesophageal submucosal glands.
- Richard Peter Owen
- , Michael Joseph White
- & Xin Lu
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Article
| Open AccessRhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16
Keratin 16 is an epithelial protein highly expressed at pressure bearing sites and during wound healing and cancer. Here the authors show that K16 interacts with the inactive protease Rhbdf2, associated with Tylosis with oesophageal cancer, and that this interaction drives increased keratinocyte proliferation.
- Thiviyani Maruthappu
- , Anissa Chikh
- & David P. Kelsell
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Article
| Open AccessMutational spectrum of Barrett’s stem cells suggests paths to initiation of a precancerous lesion
Barrett’s oesophagus is a precancerous intestinal metaplasia that can progress to oesophageal adenocarcinoma. In this study, the authors isolate and characterize human Barrett’s stem cells and identify a specific genomic pedigree that supports the potential role of these cells as precursors of oesophageal adenocarcinoma.
- Yusuke Yamamoto
- , Xia Wang
- & Wa Xian
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Article |
GWAS identifies four novel eosinophilic esophagitis loci
Eosinophilic oesophagitis (EoE) is an allergic, inflammatory disorder of the oesophagus. Here the authors carry out a genome-wide association study in over 5,000 individuals and identify four genetic loci that affect the onset of EoE.
- Patrick M. A. Sleiman
- , Mei-Lun Wang
- & Hakon Hakonarson