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Evolution of Barrett’s esophagus through space and time at single-crypt and whole-biopsy levels

Author

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  • Pierre Martinez

    (Queen Mary University of London, Charterhouse Square
    Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon)

  • Diego Mallo

    (Biodesign Institute, Arizona State University)

  • Thomas G. Paulson

    (Fred Hutchinson Cancer Research Center)

  • Xiaohong Li

    (Fred Hutchinson Cancer Research Center)

  • Carissa A. Sanchez

    (Fred Hutchinson Cancer Research Center)

  • Brian J. Reid

    (Fred Hutchinson Cancer Research Center
    University of Washington)

  • Trevor A. Graham

    (Queen Mary University of London, Charterhouse Square)

  • Mary K. Kuhner

    (University of Washington)

  • Carlo C. Maley

    (Biodesign Institute, Arizona State University
    Arizona State University)

Abstract

The low risk of progression of Barrett’s esophagus (BE) to esophageal adenocarcinoma can lead to over-diagnosis and over-treatment of BE patients. This may be addressed through a better understanding of the dynamics surrounding BE malignant progression. Although genetic diversity has been characterized as a marker of malignant development, it is still unclear how BE arises and develops. Here we uncover the evolutionary dynamics of BE at crypt and biopsy levels in eight individuals, including four patients that experienced malignant progression. We assay eight individual crypts and the remaining epithelium by SNP array for each of 6–11 biopsies over 2 time points per patient (358 samples in total). Our results indicate that most Barrett’s segments are clonal, with similar number and inferred rates of alterations observed for crypts and biopsies. Divergence correlates with geographical location, being higher near the gastro-esophageal junction. Relaxed clock analyses show that genomic instability precedes and is enhanced by genome doubling. These results shed light on the clinically relevant evolutionary dynamics of BE.

Suggested Citation

  • Pierre Martinez & Diego Mallo & Thomas G. Paulson & Xiaohong Li & Carissa A. Sanchez & Brian J. Reid & Trevor A. Graham & Mary K. Kuhner & Carlo C. Maley, 2018. "Evolution of Barrett’s esophagus through space and time at single-crypt and whole-biopsy levels," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02621-x
    DOI: 10.1038/s41467-017-02621-x
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    Cited by:

    1. Thomas G. Paulson & Patricia C. Galipeau & Kenji M. Oman & Carissa A. Sanchez & Mary K. Kuhner & Lucian P. Smith & Kevin Hadi & Minita Shah & Kanika Arora & Jennifer Shelton & Molly Johnson & Andre Co, 2022. "Somatic whole genome dynamics of precancer in Barrett’s esophagus reveals features associated with disease progression," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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