TY - JOUR
T1 - Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus
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 - Kate, Fiebo J W Ten
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
AU - Graham, Trevor A.
AU - Krishnadath, Kausilia K.
N1 - Funding Information:
Higher Education Funding Council for England (HEFCE). C.C.M. was supported in part by NIH grants P01 CA91955, R01 CA149566, R01 CA170595, R01 CA185138 and R01 CA140657
PY - 2016/8/19
Y1 - 2016/8/19
N2 - 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.
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 â € benign' Barrett's lesions is predetermined, with important implications for surveillance programs.
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U2 - 10.1038/ncomms12158
DO - 10.1038/ncomms12158
M3 - Article
C2 - 27538785
AN - SCOPUS:84983233354
SN - 2041-1723
VL - 7
JO - Nature communications
JF - Nature communications
M1 - 12158
ER -