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Fixation and Spread...
Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium
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- Nicholson, Anna M. (author)
- Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England
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- Olpe, Cora (author)
- Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England;Cambridge Stem Cell Inst, Wellcome Trust Med Res Council, Cambridge, England
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- Hoyle, Alice (author)
- Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England
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- Thorsen, Ann-Sofie (author)
- Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England
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- Rus, Teja (author)
- Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England
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- Colombe, Mathilde (author)
- Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England
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- Brunton-Sim, Roxanne (author)
- Norwich Res Pk BioRepository, James Watson Rd, Norwich NR4 7UQ, Norfolk, England
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- Kemp, Richard (author)
- Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England
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- Marks, Kate (author)
- St James Univ Hosp, Pathol & Tumour Biol, Level 4,Wellcome Trust Brenner Bldg,Beckett St, Leeds LS9 7TF, W Yorkshire, England
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- Quirke, Phil (author)
- St James Univ Hosp, Pathol & Tumour Biol, Level 4,Wellcome Trust Brenner Bldg,Beckett St, Leeds LS9 7TF, W Yorkshire, England
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- Malhotra, Shalini (author)
- CUHFT, Dept Histopathol, Box 235, Cambridge, England
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- ten Hoopen, Rogier (author)
- CUHFT, Dept Histopathol, Box 235, Cambridge, England
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- Ibrahim, Ashraf (author)
- CUHFT, Dept Histopathol, Box 235, Cambridge, England
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- Lindskog, Cecilia (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Myers, Meagan B. (author)
- US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, HFT 120,3900 NCTR Rd, Jefferson, AR 72079 USA
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- Parsons, Barbara (author)
- US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, HFT 120,3900 NCTR Rd, Jefferson, AR 72079 USA
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- Tavare, Simon (author)
- Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England
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- Wilkinson, Mark (author)
- Norwich Res Pk BioRepository, James Watson Rd, Norwich NR4 7UQ, Norfolk, England
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- Morrissey, Edward (author)
- Univ Oxford, John Radcliffe Hosp, MRC Weatherall Inst Mol Med, Oxford OX3 9DS, England
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- Winton, Douglas J. (author)
- Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England
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(creator_code:org_t)
- CELL PRESS, 2018
- 2018
- English.
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In: Cell Stem Cell. - : CELL PRESS. - 1934-5909 .- 1875-9777. ; 22:6, s. 909-918.e8
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Abstract
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- We investigated the means and timing by which mutations become fixed in the human colonic epithelium by visualizing somatic clones and mathematical inference. Fixation requires two sequential steps. First, one of approximately seven active stem cells residing within each colonic crypt has to be mutated. Second, the mutated stem cell has to replace neighbors to populate the entire crypt in a process that takes several years. Subsequent clonal expansion due to crypt fission is infrequent for neutral mutations (around 0.7% of all crypts undergo fission in a single year). Pro-oncogenic mutations subvert both stem cell replacement to accelerate fixation and clonal expansion by crypt fission to achieve high mutant allele frequencies with age. The benchmarking of these behaviors allows the advantage associated with different gene-specific mutations to be compared irrespective of the cellular mechanisms by which they are conferred.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Nicholson, Anna ...
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Olpe, Cora
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Hoyle, Alice
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Thorsen, Ann-Sof ...
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Rus, Teja
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Colombe, Mathild ...
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show more...
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Brunton-Sim, Rox ...
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Kemp, Richard
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Marks, Kate
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Quirke, Phil
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Malhotra, Shalin ...
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ten Hoopen, Rogi ...
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Ibrahim, Ashraf
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Lindskog, Cecili ...
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Myers, Meagan B.
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Parsons, Barbara
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Tavare, Simon
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Wilkinson, Mark
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Morrissey, Edwar ...
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Winton, Douglas ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
- Articles in the publication
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Cell Stem Cell
- By the university
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Uppsala University