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Transformation of Barrett's esophagus stem cell, gastric cardia stem cells and normal esophagus stem cells

ABSTRACT: Barrett’s esophagus confers significant risk of esophageal adenocarcinoma. We have established the cloning of patient-matched stem cells of Barrett’s, gastric, and esophageal epithelium. Transplantation of transformed Barrett’s stem cells yielded tumors with hallmarks of esophageal adenocarcinoma, whereas transformed esophageal stem cells produced squamous cell carcinomas. These findings define a stem cell target in a precancerous lesion for preemptive therapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE64894 | GEO | 2015/10/01

SECONDARY ACCESSION(S): PRJNA272405

REPOSITORIES: GEO

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Cloning Barrett’s esophagus stem cells

Project description:Barrett’s esophagus is a precancerous lesion that confers a significant risk of esophageal adenocarcinoma. Strategies for selective eradication of Barrett’s have been stymied by our inability to identify the Barrett’s stem cell. Here we employ novel technologies to clone patient-matched stem cells of Barrett’s, gastric, and esophageal epithelium. Genomic analyses of Barrett’s stem cells reveal a patient-specific mutational spectrum ranging from low somatic variation similar to patient-matched gastric epithelial stem cells to ones marked by extensive heterozygous alteration of genes implicated in tumor suppression, epithelial planarity, and epigenetic regulation. Transplantation of transformed Barrett’s stem cells yields tumors with hallmarks of esophageal adenocarcinoma, whereas transformed esophageal stem cells yield squamous cell carcinomas. Thus Barrett’s develops from cells distinct from local eponymous epithelia, emerges without obvious driver mutations, and likely progresses through and from the generation of dominant clones. These findings define a stem cell target for preemptive therapies of a precancerous lesion.

2015-10-01 | GSE49292 | GEO

Cell cloning of Barrett's esophagus stem cell, gastric cardia stem cells and normal esophagus stem cells

Project description:Barrett’s esophagus confers significant risk of esophageal adenocarcinoma. We have established the cloning of patient-matched stem cells of Barrett’s, gastric, and esophageal epithelium. Barrett's esophagus stem cells (BE), gastric cardia stem cells (GC) and normal esophagus stem cells (Eso) from 12 patients were cloned (For BE: 12 patients, GC: 12 patients and Eso: 2 patients). Keratin 5 positive and Keratin 7 positive cells were cloned from human fetal esophageal epithelium. Using air liquid interface culture system, stem cells were induced to differentiate into mature epithelial structures.

2015-10-01 | GSE65013 | GEO

GLOBAL CHANGES IN GENE EXPRESSION OF BARRETT'S ESOPHAGUS COMPARED TO NORMAL SQUAMOUS ESOPHAGUS AND GASTRIC CARDIA TISSUES

Project description:Barrett’s esophagus (BE) is a metaplastic precursor lesion of esophageal adenocarcinoma (EA), the most rapidly increasing cancer in western societies. While the prevalence of BE is increasing, the vast majority of EA occurs in patients with undiagnosed BE. Thus, we sought to identify genes that are altered in BE compared to the normal mucosa of the esophagus, and which may be potential biomarkers for the development or diagnosis of BE. We performed gene expression analysis using HG-U133A Affymetrix chips on fresh frozen tissue samples of Barrett’s metaplasia and matched normal mucosa from squamous esophagus (NE) and gastric cardia (NC) in 43 BE patients.

2014-04-15 | E-GEOD-39491 | biostudies-arrayexpress

GLOBAL CHANGES IN GENE EXPRESSION OF BARRETT'S ESOPHAGUS COMPARED TO NORMAL SQUAMOUS ESOPHAGUS AND GASTRIC CARDIA TISSUES

2014-04-15 | GSE39491 | GEO

Gene expression profiling of Barrett's esophagus, adenocarcinoma, esophageal squamous epithelium and squamous cell carcinoma

Project description:The aim of this study is to generate and validate biomarkers to stratify patients with Barrett’s esophagus in terms of risk for developing cancer. We studied gene expression profiling in 69 frozen specimens, consisting of esophageal squamous epithelium from 19 healthy subjects, 20 specimens from patients with Barrett’s esophagus and 21 cases of esophageal adenocarcinoma, 9 cased of esophageal squamous cell carcinoma by whole genome microarray analysis. Laser capture microdissection technique was applied to procure cells from defined regions of Barrett’s esophagus metaplasia and esophageal adenocarcinoma. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent cohort consisting of 42 cases. Furthermore, immunohistochemistry was performed using antibodies to two selected target molecules on a third independent cohort of 36 specimens, consisting of 36 cases. A total of 1176 genes were associated significantly with esophageal adenocarcinoma. The expression pattern of a 4 gene signature with the highest discriminant score based on linear discriminant analysis (GeneSpring GX10.2), was identified and validated by qRT-PCR in independent cohort. Gene expression profiling of 20 specimens of Barrett's esophagus patients, 21 specimens of adenocarcinoma patients and 19 biopsies from patients with normal esophageal squamous epithelium, 9 specimens of squamous cell carcinoma were studied.

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Copy number variation analysis of human Barrett's esophagus stem cells (HumanOmniZhongHua-8 v1.1 Beadchip)

Project description:Barrett’s esophagus confers significant risk of esophageal adenocarcinoma. We have established the cloning system of patient-matched stem cells of Barrett’s esophagus and gastric cardia. Barrett's esophagus (BE) stem cells and gastric cardia (GC) stem cells from 12 patients were cloned. To analyze copy number variation in BE and GC stem cells, we have performed SNP array. It has shown that deletions such as p16 and FHIT in BE stem cells are significantly detected, while amplifications in BE stem cells are not. Also, we found some of BE stem cells did not share these deletions, suggesting emerging of BE does not require specific CNV.

2016-01-13 | GSE68663 | GEO

Copy number variation analysis of human Barrett's esophagus stem cells (HumanOmniZhongHua-8 v1.0 Beadchip)

2016-01-13 | GSE68662 | GEO

Gene expression profiling of Barrett's esophagus, adenocarcinoma, esophageal squamous epithelium and squamous cell carcinoma

2013-10-18 | GSE26886 | GEO

Barrett's esophageal tissues and esophageal adenocarcinoma specimens

Project description:This SuperSeries is composed of the following subset Series: GSE37200: Gene expression profiling of Barrett’s esophageal tissues and esophageal adenocarcinoma specimens GSE37201: Gene expression profiling of esophageal adenocarcinoma Refer to individual Series

2012-04-10 | E-GEOD-37203 | biostudies-arrayexpress

Barrett's esophagus

Project description:Barrett's esophagus transcriptome was analysed and compared with Barrett's esophagus primary cell culture and esophageal adenocarcinoma. Keywords: SAGE analysis to compare tissues Barrett's esophagus biopsy was taken from 1 male metaplastic Barrett's esophagus patient. Barrett's esophagus primary cell culture was cultures from a biopsy taken from a Barrett's esophagus patient and cultured for about 4 to 5 weeks. Esophageal adenocarcinoma was taken from a patient known to have cancer and previously Barrett's esophagus

2006-06-28 | E-GEOD-5155 | biostudies-arrayexpress

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