Supported by the Dutch Cancer Society (KWF) and Cancer Research UK (CR-UK). This work was supported by Cancer Research UK (grant number A14895

Cereser, B

Gay, LJ

Graham, TA

Jansen, M

Lavery, DL

Martinez, P

McDonald, SAC

Meijer, SL

Novelli, MR

Rodriguez-Justo, M

Wright, NA

PubMed

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

McDonald, SA

Spiral - Imperial College Digital Repository

English

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

Queen Mary Research Online

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. 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. 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. Our data demonstrate the premalignant potential of metaplastic columnar epithelium without goblet cells in the context of Barrett's oesophagu

Lavery, Danielle L.

Martinez, Pierre

Gay, Laura J.

Cereser, Biancastella

Novelli, Marco R.

Rodriguez-Justo, Manuel

Meijer, Sybren L.

Graham, Trevor A.

McDonald, Stuart A. C.

Wright, Nicholas A.

Jansen, Marnix

NARCIS 

Danielle L Lavery

Pierre Martinez

Laura J Gay

Biancastella Cereser

Marco R Novelli

Manuel Rodriguez-Justo

Sybren L Meijer

Trevor A Graham

Stuart A C McDonald

Nicholas A Wright

Marnix Jansen

Crossref

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

UCL Discovery

https://qmro.qmul.ac.uk/xmlui/bitstream/handle/123456789/15434/Graham%20Evolution%20of%20oesophageal%20adenocarcinoma%202015%20Published.pdf?sequence=1

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

Abstract

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Spiral - Imperial College Digital Repository

Queen Mary Research Online

NARCIS

Crossref

UCL Discovery