Fixation and spread of somatic mutations in adult human colonic epithelium
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 muta...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2018
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| _version_ | 1826290152472838144 |
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| author | Nicholson, A Olpe, C Hoyle, A Thorsen, A Rus, T Colombé, M Brunton-Sim, R Kemp, R Marks, K Quirke, P Malhotra, S Ten Hoopen, R Ibrahim, A Lindskog, C Myers, M Parsons, B Tavaré, S Wilkinson, M Morrissey, E Winton, D |
| author_facet | Nicholson, A Olpe, C Hoyle, A Thorsen, A Rus, T Colombé, M Brunton-Sim, R Kemp, R Marks, K Quirke, P Malhotra, S Ten Hoopen, R Ibrahim, A Lindskog, C Myers, M Parsons, B Tavaré, S Wilkinson, M Morrissey, E Winton, D |
| author_sort | Nicholson, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T02:39:49Z |
| format | Journal article |
| id | oxford-uuid:aa0c8363-47c0-4fd2-ab05-8052792f365f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:39:49Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:aa0c8363-47c0-4fd2-ab05-8052792f365f2022-03-27T03:12:40ZFixation and spread of somatic mutations in adult human colonic epitheliumJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:aa0c8363-47c0-4fd2-ab05-8052792f365fEnglishSymplectic Elements at OxfordElsevier2018Nicholson, AOlpe, CHoyle, AThorsen, ARus, TColombé, MBrunton-Sim, RKemp, RMarks, KQuirke, PMalhotra, STen Hoopen, RIbrahim, ALindskog, CMyers, MParsons, BTavaré, SWilkinson, MMorrissey, EWinton, DWe 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. |
| spellingShingle | Nicholson, A Olpe, C Hoyle, A Thorsen, A Rus, T Colombé, M Brunton-Sim, R Kemp, R Marks, K Quirke, P Malhotra, S Ten Hoopen, R Ibrahim, A Lindskog, C Myers, M Parsons, B Tavaré, S Wilkinson, M Morrissey, E Winton, D Fixation and spread of somatic mutations in adult human colonic epithelium |
| title | Fixation and spread of somatic mutations in adult human colonic epithelium |
| title_full | Fixation and spread of somatic mutations in adult human colonic epithelium |
| title_fullStr | Fixation and spread of somatic mutations in adult human colonic epithelium |
| title_full_unstemmed | Fixation and spread of somatic mutations in adult human colonic epithelium |
| title_short | Fixation and spread of somatic mutations in adult human colonic epithelium |
| title_sort | fixation and spread of somatic mutations in adult human colonic epithelium |
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