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Dynamic clonal equilibrium and predetermined cancer risk in Barrett’s oesophagus

Author

Listed:
  • Pierre Martinez

    (Evolution and Cancer Laboratory, Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London)

  • Margriet R. Timmer

    (Academic Medical Center—University of Amsterdam
    Center for Experimental and Molecular Medicine, Academic Medical Center—University of Amsterdam)

  • Chiu T. Lau

    (Academic Medical Center—University of Amsterdam
    Center for Experimental and Molecular Medicine, Academic Medical Center—University of Amsterdam)

  • Silvia Calpe

    (Academic Medical Center—University of Amsterdam
    Center for Experimental and Molecular Medicine, Academic Medical Center—University of Amsterdam)

  • Maria del Carmen Sancho-Serra

    (Academic Medical Center—University of Amsterdam
    Center for Experimental and Molecular Medicine, Academic Medical Center—University of Amsterdam)

  • Danielle Straub

    (Academic Medical Center—University of Amsterdam
    Center for Experimental and Molecular Medicine, Academic Medical Center—University of Amsterdam)

  • Ann-Marie Baker

    (Evolution and Cancer Laboratory, Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London)

  • Sybren L. Meijer

    (Academic Medical Center—University of Amsterdam)

  • Fiebo J. W. ten Kate

    (Academic Medical Center—University of Amsterdam)

  • Rosalie C. Mallant-Hent

    (Flevoziekenhuis
    Gastroenterological Association)

  • Anton H. J. Naber

    (Gastroenterological Association
    Tergooiziekenhuizen)

  • Arnoud H. A. M. van Oijen

    (Gastroenterological Association
    Medisch Centrum)

  • Lubbertus C. Baak

    (Gastroenterological Association
    Onze Lieve Vrouwe Gasthuis)

  • Pieter Scholten

    (Gastroenterological Association
    Sint Lucas Andreas Ziekenhuis)

  • Clarisse J. M. Böhmer

    (Gastroenterological Association
    Spaarne Ziekenhuis)

  • Paul Fockens

    (Academic Medical Center—University of Amsterdam)

  • Jacques J. G. H. M. Bergman

    (Academic Medical Center—University of Amsterdam
    Gastroenterological Association)

  • Carlo C. Maley

    (Biodesign Institute, School of Life Sciences, Arizona State University)

  • Trevor A. Graham

    (Evolution and Cancer Laboratory, Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London)

  • Kausilia K Krishnadath

    (Academic Medical Center—University of Amsterdam
    Center for Experimental and Molecular Medicine, Academic Medical Center—University of Amsterdam
    Gastroenterological Association)

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 cm2 (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.

Suggested Citation

  • Pierre Martinez & Margriet R. Timmer & Chiu T. Lau & Silvia Calpe & Maria del Carmen Sancho-Serra & Danielle Straub & Ann-Marie Baker & Sybren L. Meijer & Fiebo J. W. ten Kate & Rosalie C. Mallant-Hen, 2016. "Dynamic clonal equilibrium and predetermined cancer risk in Barrett’s oesophagus," Nature Communications, Nature, vol. 7(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12158
    DOI: 10.1038/ncomms12158
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    Cited by:

    1. Mohammadamin Edrisi & Xiru Huang & Huw A. Ogilvie & Luay Nakhleh, 2023. "Accurate integration of single-cell DNA and RNA for analyzing intratumor heterogeneity using MaCroDNA," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. S J M Hoefnagel & N Mostafavi & M R Timmer & C T Lau & S L Meijer & K K Wang & K K Krishnadath, 2020. "A genomic biomarker-based model for cancer risk stratification of non-dysplastic Barrett’s esophagus patients after extended follow up; results from Dutch surveillance cohorts," PLOS ONE, Public Library of Science, vol. 15(4), pages 1-17, April.

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