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

Nature Communications
Pierre MartinezCarlo C Maley

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.

Associated Datasets

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Citations

Oct 20, 2018·Science·Iñigo MartincorenaPhilip H Jones
Dec 13, 2018·Bioinformatics·Lucian P SmithMary K Kuhner
Sep 25, 2019·Nature Reviews. Genetics·Uri Ben-David, Angelika Amon
Sep 19, 2020·Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus·N F FreiR E Pouw
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Jun 29, 2018·Digestive Diseases and Sciences·Nicholas A Wright
Dec 2, 2020·Nature Reviews. Genetics·Erez PersiEugene V Koonin
Jan 16, 2021·Science·T StadlerM P H Stumpf
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Nov 4, 2021·Nature Reviews. Gastroenterology & Hepatology·Melissa SchmidtTrevor A Graham
Nov 18, 2021·Cancer Research·Guido LenzKarine R Begnini

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Datasets Mentioned

BETA
GSE99431

Methods Mentioned

BETA
biopsies
chromosomal aberrations
biopsy
surgical resection
flow cytometry
genetic modifications
Assay

Software Mentioned

copynumber
phangorn
BEAST
pennCNV
Illumina GenomeStudio
ASCAT

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