title: Evolution of oesophageal adenocarcinoma from metaplastic columnar epithelium without goblet cells in Barrett's oesophagus.
abstract: 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 oesophagus.
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Lavery
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Pierre
authors.initials: P
authors.lastname: Martinez
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Gay
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Biancastella
authors.initials: B
authors.lastname: Cereser
authors.affiliation: Department of Pathology, University College London, London, UK.
authors.forename: Marco R
authors.initials: MR
authors.lastname: Novelli
authors.affiliation: Department of Pathology, University College London, London, UK.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodriguez-Justo
authors.affiliation: Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Sybren L
authors.initials: SL
authors.lastname: Meijer
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Graham
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Stuart A C
authors.initials: SA
authors.lastname: McDonald
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Wright
authors.affiliation: Barts Cancer Institute, Queen Mary University of London, London, UK Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Marnix
authors.initials: M
authors.lastname: Jansen
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D001471:Barrett Esophagus / Q000150:complications*; D001706:Biopsy; D003576:Electron Transport Complex IV; D004848:Epithelium / Q000473:pathology; D004938:Esophageal Neoplasms / Q000473:pathology*; D059472:Exome; D005260:Female; D020397:Goblet Cells / Q000473:pathology*; D006801:Humans; D008679:Metaplasia / Q000473:pathology; D008875:Middle Aged; D008928:Mitochondria; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D003576:Electron Transport Complex IV
keywords: BARRETT'S CARCINOMA; BARRETT'S METAPLASIA; BARRETT'S OESOPHAGUS