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

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-Hent, Anton H J Naber, Arnoud H A M Van Oijen, Lubbertus C. Baak, Pieter Scholten, Clarisse J M Böhmer, Paul Fockens, Jacques J G H M Bergman, Carlo Maley, Trevor A. Graham, Kausilia K. Krishnadath

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37 Scopus citations

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 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 â € benign' Barrett's lesions is predetermined, with important implications for surveillance programs.

Original languageEnglish (US)
Article number12158
JournalNature Communications
Volume7
DOIs
StatePublished - Aug 19 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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    Martinez, P., Timmer, M. R., Lau, C. T., Calpe, S., Sancho-Serra, M. D. C., Straub, D., Baker, A. M., Meijer, S. L., Kate, F. J. W. T., Mallant-Hent, R. C., Naber, A. H. J., Van Oijen, A. H. A. M., Baak, L. C., Scholten, P., Böhmer, C. J. M., Fockens, P., Bergman, J. J. G. H. M., Maley, C., Graham, T. A., & Krishnadath, K. K. (2016). Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus. Nature Communications, 7, [12158]. https://doi.org/10.1038/ncomms12158