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Using DNA methylation to detect dysplasia/early neoplasia in Barrett's carcinogenesis

ABSTRACT: Dysplasia and early cancer are hard to detect in endoscopic biopsies and hence this study was carried out to evaluate the biomarker potential of DNA methylation to detect dyspasia and early cancer in Barrett's esophaghus patients. Bisulfite converted genomic DNA was hybridized onto Illumina 27k methylation arrays.

ORGANISM(S): Homo sapiens

PROVIDER: GSE32925 | GEO | 2013/01/28

SECONDARY ACCESSION(S): PRJNA146489

REPOSITORIES: GEO

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Using DNA methylation to detect dysplasia/early neoplasia in Barrett's carcinogenesis

Project description:Dysplasia and early cancer are hard to detect in endoscopic biopsies and hence this study was carried out to evaluate the biomarker potential of DNA methylation to detect dyspasia and early cancer in Barrett's esophaghus patients. Bisulfite converted genomic DNA was hybridized onto Illumina 27k methylation arrays. 22 Barrett's esophagus (BE) and 2 Duodenum vs. 24 esophageal adenocarcinoma (EAC)

2013-01-28 | E-GEOD-32925 | biostudies-arrayexpress

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DNA methylation as an adjunct to histopathology to detect prevalent, inconspicuous dysplasia and early-stage neoplasia in Barrett's esophagus.

Project description:PURPOSE:Endoscopic surveillance of Barrett's esophagus is problematic because dysplasia/early-stage neoplasia is frequently invisible and likely to be missed because of sampling bias. Molecular abnormalities may be more diffuse than dysplasia. The aim was therefore to test whether DNA methylation, especially on imprinted and X-chromosome genes, is able to detect dysplasia/early-stage neoplasia. EXPERIMENTAL DESIGN:27K methylation arrays were used to find genes best able to differentiate between 22 Barrett's esophagus and 24 esophageal adenocarcinoma (EAC) samples. These were validated using pyrosequencing on a retrospective cohort (60 Barrett's esophagus, 36 dysplastic, and 90 EAC) and then in a prospective multicenter study (98 Barrett's esophagus patients, including 28 dysplastic and 9 early EAC) designed to utilize biomarkers to stratify patients according to their prevalent dysplasia/EAC status. RESULTS:Genes (23%) on the array, including 7% of X-linked and 69% of imprinted genes, have shown statistically significant changes in methylation in EAC versus Barrett's esophagus (Wilcoxon P < 0.05). 6/7 selected candidate genes were successfully internally (Pearson's P < 0.01) and externally validated (ANOVA P < 0.001). Four genes (SLC22A18, PIGR, GJA12, and RIN2) showed the greatest area under curve (0.988) to distinguish between Barrett's esophagus and dysplasia/EAC in the retrospective cohort. This methylation panel was able to stratify patients from the prospective cohort into three risk groups based on the number of genes methylated (low risk: <2 genes, intermediate: 2, and high: >2). CONCLUSION:Widespread DNA methylation changes were observed in Barrett's carcinogenesis including ?70% of known imprinted genes. A four-gene methylation panel stratified patients with Barrett's esophagus into three risk groups with potential clinical utility.

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Project description:mucosal biopsies were taken from patients at pre and post-argon plasma coagulation (APC) ablation of Barrett's oesophagus, and from healthy controls. Total RNA was extracted using Trizol. miRNA was reversed transcribed using a TaqMan® microRNA Reverse Transcription Kit (Life technologies, #4366596). miRNA profiling was performed with a high throughput TaqMan® OpenArray® Human microRNA panel (Life technologies, #4461104). The panel consisted of probes for 754 human miRNAs that are based on miRNA sequences derived from Sanger miRBase v14. Endoscopic surveillance remains the mainstay of cancer prevention in individuals with Barrett’s oesophagus, and definitive management by surgery or endoscopy is reserved for high grade dysplasia or cancer. There are several endoscopic treatments that are widely used for Barrett’s oesophagus, including argon plasma coagulation (APC). The normality of the regenerated neosquamous epithelium after ablation has been called into question. In the current study we profiled global microRNA expression in oesophageal mucosa before and after ablation of Barrett’s oesophagus using Argon plasma coagulation. Our aim was to investigate differences in microRNA expression between neosquamous and normal squamous tissues.

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