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

Research output: Contribution to journalArticle

34 Citations (Scopus)

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

Fingerprint

esophagus
Barrett Esophagus
cancer
Cytology
surveillance
Brushes
resolution cell
cytology
Clonal Evolution
biological diversity
intervals
neoplasms
Neoplasms
Fluorescence
brushes
loci
Fluorescence In Situ Hybridization
progressions
lesions
set theory

ASJC Scopus subject areas

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

Cite this

Martinez, P., Timmer, M. R., Lau, C. T., Calpe, S., Sancho-Serra, M. D. C., Straub, D., ... 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

Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus. / Martinez, Pierre; Timmer, Margriet R.; Lau, Chiu T.; Calpe, Silvia; Sancho-Serra, Maria Del Carmen; Straub, Danielle; Baker, Ann Marie; Meijer, Sybren L.; Kate, Fiebo J W Ten; Mallant-Hent, Rosalie C.; Naber, Anton H J; Van Oijen, Arnoud H A M; Baak, Lubbertus C.; Scholten, Pieter; Böhmer, Clarisse J M; Fockens, Paul; Bergman, Jacques J G H M; Maley, Carlo; Graham, Trevor A.; Krishnadath, Kausilia K.

In: Nature Communications, Vol. 7, 12158, 19.08.2016.

Research output: Contribution to journalArticle

Martinez, P, Timmer, MR, Lau, CT, Calpe, S, Sancho-Serra, MDC, Straub, D, Baker, AM, Meijer, SL, Kate, FJWT, Mallant-Hent, RC, Naber, AHJ, Van Oijen, AHAM, Baak, LC, Scholten, P, Böhmer, CJM, Fockens, P, Bergman, JJGHM, Maley, C, Graham, TA & Krishnadath, KK 2016, 'Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus', Nature Communications, vol. 7, 12158. https://doi.org/10.1038/ncomms12158
Martinez P, Timmer MR, Lau CT, Calpe S, Sancho-Serra MDC, Straub D et al. Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus. Nature Communications. 2016 Aug 19;7. 12158. https://doi.org/10.1038/ncomms12158
Martinez, Pierre ; Timmer, Margriet R. ; Lau, Chiu T. ; Calpe, Silvia ; Sancho-Serra, Maria Del Carmen ; Straub, Danielle ; Baker, Ann Marie ; Meijer, Sybren L. ; Kate, Fiebo J W Ten ; Mallant-Hent, Rosalie C. ; Naber, Anton H J ; Van Oijen, Arnoud H A M ; Baak, Lubbertus C. ; Scholten, Pieter ; Böhmer, Clarisse J M ; Fockens, Paul ; Bergman, Jacques J G H M ; Maley, Carlo ; Graham, Trevor A. ; Krishnadath, Kausilia K. / Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus. In: Nature Communications. 2016 ; Vol. 7.
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