Defining Stem Cell Dynamics in Models of Intestinal Tumor Initiation

Louis Vermeulen, Edward Morrissey, Maartje van der Heijden, Anna M. Nicholson, Andrea Sottoriva, Simon Buczacki, Richard Kemp, Simon Tavaré, Douglas J. Winton

Research output: Contribution to journalArticleAcademicpeer-review

307 Citations (Scopus)

Abstract

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
Original languageEnglish
Pages (from-to)995-998
JournalScience
Volume342
Issue number6161
DOIs
Publication statusPublished - 2013

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