Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium.
Cell Stem Cell
; 22(6): 909-918.e8, 2018 Jun 01.
Article
in En
| MEDLINE
| ID: mdl-29779891
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colon
/
Antigens, Nuclear
/
Epithelial Cells
/
Epithelium
/
Monoamine Oxidase
/
Mutation
Type of study:
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Child
/
Humans
/
Middle aged
Language:
En
Journal:
Cell Stem Cell
Year:
2018
Document type:
Article
Affiliation country:
United kingdom