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 C. Maley; Trevor A. Graham; Kausilia K. Krishnadath

doi:https://doi.org/10.1038/ncomms12158

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 C. Maley, Trevor A. Graham, Kausilia K. Krishnadath

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

Original language	English
Pages (from-to)	12158
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12158
Publication status	Published - 2016

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https://doi.org/10.1038/ncomms12158

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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., ten Kate, F. J. W., 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. 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

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title = "Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus",

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 'benign' Barrett's lesions is predetermined, with important implications for surveillance programs",

author = "Pierre Martinez and Timmer, {Margriet R.} and Lau, {Chiu T.} and Silvia Calpe and Sancho-Serra, {Maria Del Carmen} and Danielle Straub and Ann-Marie Baker and Meijer, {Sybren L.} and {ten Kate}, {Fiebo J. W.} and Mallant-Hent, {Rosalie C.} and Naber, {Anton H. J.} and {van Oijen}, {Arnoud H. A. M.} and Baak, {Lubbertus C.} and Pieter Scholten and B{\"o}hmer, {Clarisse J. M.} and Paul Fockens and Bergman, {Jacques J. G. H. M.} and Maley, {Carlo C.} and Graham, {Trevor A.} and Krishnadath, {Kausilia K.}",

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Martinez, P, Timmer, MR, Lau, CT, Calpe, S, Sancho-Serra, MDC, Straub, D, Baker, A-M, Meijer, SL, ten Kate, FJW, Mallant-Hent, RC, Naber, AHJ, van Oijen, AHAM, Baak, LC, Scholten, P, Böhmer, CJM, Fockens, P , Bergman, JJGHM, Maley, CC, Graham, TA & Krishnadath, KK 2016, 'Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus', Nature communications, vol. 7, pp. 12158. https://doi.org/10.1038/ncomms12158

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AU - Martinez, Pierre

AU - Timmer, Margriet R.

AU - Lau, Chiu T.

AU - Calpe, Silvia

AU - Sancho-Serra, Maria Del Carmen

AU - Straub, Danielle

AU - Baker, Ann-Marie

AU - Meijer, Sybren L.

AU - ten Kate, Fiebo J. W.

AU - Mallant-Hent, Rosalie C.

AU - Naber, Anton H. J.

AU - van Oijen, Arnoud H. A. M.

AU - Baak, Lubbertus C.

AU - Scholten, Pieter

AU - Böhmer, Clarisse J. M.

AU - Fockens, Paul

AU - Bergman, Jacques J. G. H. M.

AU - Maley, Carlo C.

AU - Graham, Trevor A.

AU - Krishnadath, Kausilia K.

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AB - 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 'benign' Barrett's lesions is predetermined, with important implications for surveillance programs

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