Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission.

ABSTRACT: The understanding of the fixation of mutations within human tissues and their subsequent clonal expansion is a considerable problem, of which little is known. We have previously shown that nononcogenic mutations in the mitochondrial genome occur in one of a number of morphologically normal colonic crypt stem cells, the progeny of which later occupy the whole crypt. We propose that these wholly mutated crypts then clonally expand by crypt fission, where each crypt divides into two mutated daughter crypts. Here we show that (i) mutated crypts in the process of fission share the same mutated mitochondrial genotype not present in neighboring cytochrome c oxidase-positive crypts (the odds of this being a random event are >or=2.48 x 10(9):1); (ii) neighboring mutated crypts have the same genotyp

SUBMITTER: Greaves LC 

PROVIDER: S-EPMC1325106 | biostudies-literature | 2006 Jan

REPOSITORIES: biostudies-literature