TY - JOUR
T1 - Defining Stem Cell Dynamics in Models of Intestinal Tumor Initiation
AU - Vermeulen, Louis
AU - Morrissey, Edward
AU - van der Heijden, Maartje
AU - Nicholson, Anna M.
AU - Sottoriva, Andrea
AU - Buczacki, Simon
AU - Kemp, Richard
AU - Tavaré, Simon
AU - Winton, Douglas J.
PY - 2013
Y1 - 2013
N2 - Cancer is a disease in which cells accumulate genetic aberrations that are believed to confer a clonal advantage over cells in the surrounding tissue. However, the quantitative benefit of frequently occurring mutations during tumor development remains unknown. We quantified the competitive advantage of Apc loss, Kras activation, and P53 mutations in the mouse intestine. Our findings indicate that the fate conferred by these mutations is not deterministic, and many mutated stem cells are replaced by wild-type stem cells after biased, but still stochastic events. Furthermore, P53 mutations display a condition-dependent advantage, and especially in colitis-affected intestines, clones harboring mutations in this gene are favored. Our work confirms the previously theoretical notion that the tissue architecture of the intestine suppresses the accumulation of mutated lineages
AB - Cancer is a disease in which cells accumulate genetic aberrations that are believed to confer a clonal advantage over cells in the surrounding tissue. However, the quantitative benefit of frequently occurring mutations during tumor development remains unknown. We quantified the competitive advantage of Apc loss, Kras activation, and P53 mutations in the mouse intestine. Our findings indicate that the fate conferred by these mutations is not deterministic, and many mutated stem cells are replaced by wild-type stem cells after biased, but still stochastic events. Furthermore, P53 mutations display a condition-dependent advantage, and especially in colitis-affected intestines, clones harboring mutations in this gene are favored. Our work confirms the previously theoretical notion that the tissue architecture of the intestine suppresses the accumulation of mutated lineages
U2 - https://doi.org/10.1126/science.1243148
DO - https://doi.org/10.1126/science.1243148
M3 - Article
C2 - 24264992
SN - 0036-8075
VL - 342
SP - 995
EP - 998
JO - Science
JF - Science
IS - 6161
ER -