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Evolution of oesophageal adenocarcinoma from metaplastic columnar epithelium without goblet cells in Barrett's oesophagus

Lavery, DL; Martinez, P; Gay, LJ; Cereser, B; Novelli, MR; Rodriguez-Justo, M; Meijer, SL; ... Jansen, M; + view all (2015) Evolution of oesophageal adenocarcinoma from metaplastic columnar epithelium without goblet cells in Barrett's oesophagus. Gut , 65 (6) pp. 907-913. 10.1136/gutjnl-2015-310748. Green open access

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Abstract

Objective Barrett's oesophagus commonly presents as a patchwork of columnar metaplasia with and without goblet cells in the distal oesophagus. The presence of metaplastic columnar epithelium with goblet cells on oesophageal biopsy is a marker of cancer progression risk, but it is unclear whether clonal expansion and progression in Barrett's oesophagus is exclusive to columnar epithelium with goblet cells. Design We developed a novel method to trace the clonal ancestry of an oesophageal adenocarcinoma across an entire Barrett's segment. Clonal expansions in Barrett's mucosa were identified using cytochrome c oxidase enzyme histochemistry. Somatic mutations were identified through mitochondrial DNA sequencing and single gland whole exome sequencing. Results By tracing the clonal origin of an oesophageal adenocarcinoma across an entire Barrett's segment through a combination of histopathological spatial mapping and clonal ordering, we find that this cancer developed from a premalignant clonal expansion in non-dysplastic (‘cardia-type’) columnar metaplasia without goblet cells. Conclusion Our data demonstrate the premalignant potential of metaplastic columnar epithelium without goblet cells in the context of Barrett's oesophagus.

Type: Article
Title: Evolution of oesophageal adenocarcinoma from metaplastic columnar epithelium without goblet cells in Barrett's oesophagus
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/gutjnl-2015-310748
Publisher version: https://doi.org/10.1136/gutjnl-2015-310748
Language: English
Additional information: This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology, Life Sciences & Biomedicine, Gastroenterology & Hepatology, INTESTINAL METAPLASIA, LINED ESOPHAGUS, CANCER-RISK, ABNORMALITIES, EXPRESSION, MANAGEMENT, MUTATIONS, JUNCTION, GLANDS, EXOME
URI: http://discovery.ucl.ac.uk/id/eprint/10046580
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