Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms12158
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Funding
- The Dutch Cancer Foundation (KWF)
- The Netherlands Organization for Scientific Research (NWO)
- Fonds NutsOhra
- European Research Council (ERC-StG)
- Gutclub foundation
- Abbott Molecular
- QMUL Research-IT
- EPSRC [EP/K000128/1]
- Cancer Research UK
- Higher Education Funding Council for England (HEFCE)
- NIH [P01 CA91955, R01 CA149566, R01 CA170595, R01 CA185138, R01 CA140657]
- CDMRP Breast Cancer Research Program Award [BC132057]
- Cancer Research UK [19771] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/K000233/1, EP/K000128/1] Funding Source: researchfish
- EPSRC [EP/K000233/1, EP/K000128/1] Funding Source: UKRI
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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.
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