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

P. Martinez,M. Timmer,C. T. Lau,S. Calpe,M. D. C. Sancho-Serra,D. Straub,A. Baker,S. Meijer,F. Kate,R. Mallant-Hent,A. Naber,A. van Oijen,L. Baak,P. Scholten,C. Böhmer,P. Fockens,J. Bergman,C. Maley,T. Graham,K. Krishnadath

Published 2016 in Nature Communications

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. Barrett’s oesophagus is thought to be a precursor lesion for oesophageal cancer, and predicting the benign lesions that progress to cancer is clinically important. Here, the authors use FISH to study the clonal evolution of Barrett’s oesophagus and show that genetic diversity and somatic mutations are present early in the benign disease.

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