title: Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus.
abstract: Surveillance of Barrett's oesophagus allows us to study the evolutionary dynamics of a human neoplasm over time. Here we use multicolour fluorescence in situ hybridization on brush cytology specimens, from two time points with a median interval of 37 months in 195 non-dysplastic Barrett's patients, and a third time point in a subset of 90 patients at a median interval of 36 months, to study clonal evolution at single-cell resolution. Baseline genetic diversity predicts progression and remains in a stable dynamic equilibrium over time. Clonal expansions are rare, being detected once every 36.8 patient years, and growing at an average rate of 1.58 cm(2) (95% CI: 0.09-4.06) per year, often involving the p16 locus. This suggests a lack of strong clonal selection in Barrett's and that the malignant potential of 'benign' Barrett's lesions is predetermined, with important implications for surveillance programs.
authors.affiliation: Evolution and Cancer Laboratory, Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ London, UK.
authors.forename: Pierre
authors.initials: P
authors.lastname: Martinez
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.|Center for Experimental and Molecular Medicine, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.
authors.forename: Margriet R
authors.initials: MR
authors.lastname: Timmer
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.|Center for Experimental and Molecular Medicine, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.
authors.forename: Chiu T
authors.initials: CT
authors.lastname: Lau
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.|Center for Experimental and Molecular Medicine, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.
authors.forename: Silvia
authors.initials: S
authors.lastname: Calpe
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.|Center for Experimental and Molecular Medicine, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.
authors.forename: Maria Del Carmen
authors.initials: Mdel C
authors.lastname: Sancho-Serra
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.|Center for Experimental and Molecular Medicine, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.
authors.forename: Danielle
authors.initials: D
authors.lastname: Straub
authors.affiliation: Evolution and Cancer Laboratory, Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ London, UK.
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Baker
authors.affiliation: Department of Pathology, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.
authors.forename: Sybren L
authors.initials: SL
authors.lastname: Meijer
authors.affiliation: Department of Pathology, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.
authors.forename: Fiebo J W Ten
authors.initials: FJ
authors.lastname: Kate
authors.affiliation: Department of Gastroenterology and Hepatology, Flevoziekenhuis, 1300 EG Almere, The Netherlands.|Gastroenterological Association, 1006 AE Amsterdam, The Netherlands.
authors.forename: Rosalie C
authors.initials: RC
authors.lastname: Mallant-Hent
authors.affiliation: Gastroenterological Association, 1006 AE Amsterdam, The Netherlands.|Department of Gastroenterology and Hepatology, Tergooiziekenhuizen, 1201 DA Hilversum, The Netherlands.
authors.forename: Anton H J
authors.initials: AH
authors.lastname: Naber
authors.affiliation: Gastroenterological Association, 1006 AE Amsterdam, The Netherlands.|Department of Gastroenterology and Hepatology, Medisch Centrum, 1800 AM Alkmaar, The Netherlands.
authors.forename: Arnoud H A M
authors.initials: AH
authors.lastname: van Oijen
authors.affiliation: Gastroenterological Association, 1006 AE Amsterdam, The Netherlands.|Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, 1091 AC Amsterdam, The Netherlands.
authors.forename: Lubbertus C
authors.initials: LC
authors.lastname: Baak
authors.affiliation: Gastroenterological Association, 1006 AE Amsterdam, The Netherlands.|Department of Gastroenterology and Hepatology, Sint Lucas Andreas Ziekenhuis, 1006 AE Amsterdam, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Scholten
authors.affiliation: Gastroenterological Association, 1006 AE Amsterdam, The Netherlands.|Department of Gastroenterology and Hepatology, Spaarne Ziekenhuis, 2134 TM Hoofddorp, The Netherlands.
authors.forename: Clarisse J M
authors.initials: CJ
authors.lastname: Böhmer
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Fockens
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.|Gastroenterological Association, 1006 AE Amsterdam, The Netherlands.
authors.forename: Jacques J G H M
authors.initials: JJ
authors.lastname: Bergman
authors.affiliation: Biodesign Institute, School of Life Sciences, Arizona State University, Tempe, Arizona 85281, USA.
authors.forename: Carlo C
authors.initials: CC
authors.lastname: Maley
authors.affiliation: Evolution and Cancer Laboratory, Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ London, UK.
authors.forename: Trevor A
authors.identifier: 0000-0001-9582-1597
authors.initials: TA
authors.lastname: Graham
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.|Center for Experimental and Molecular Medicine, Academic Medical Center-University of Amsterdam, 1100 DD Amsterdam, The Netherlands.|Gastroenterological Association, 1006 AE Amsterdam, The Netherlands.
authors.forename: Kausilia K
authors.initials: KK
authors.lastname: Krishnadath
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D001706:Biopsy; D063646:Carcinogenesis / Q000235:genetics*; D060965:Clonal Evolution; D018450:Disease Progression; D062665:Epidemiological Monitoring; D004938:Esophageal Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D004945:Esophagoscopy; D004947:Esophagus / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D059010:Single-Cell Analysis