The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission
Open accessAbstract
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 ≥2.48 × 10 9 :1); ( ii ) neighboring mutated crypts have the same genotype, which is different from adjacent cytochrome c oxidase-positive crypts; ( iii ) mutated crypts are clustered together throughout the colon; and ( iv ) patches of cytochrome c oxidase-deficient crypts increase in size with age. We thus demonstrate definitively that crypt fission is the mechanism by which mutations spread in the normal human colon. This has important implications for the biology of the normal adult human colon and possibly for the growth and spread of colorectal neoplasms.
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Cites
Mitochondrial DNA mutations in human disease
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Mitochondrial DNA mutations in human colonic crypt stem cells
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Self-citationThe Protein Information Resource
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Mutations in the p53 gene: An early marker of neoplastic progression in ulcerative colitis
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Cited by
Barker, N., van de Wetering, M., & Clevers, H. (2008) · Genes & Development · doi:10.1101/gad.1674008 · Cited by 629
An Attempt to Prevent Senescence: A Mitochondrial Approach
Skulachev, V. P., Anisimov, V. N., Antonenko, Y. N., Bakeeva, L. E., Chernyak, B. V., Erichev, V. P., Filenko, O. F., Kalinina, N. I., Kapelko, V. I., Kolosova, N. G., et al. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.12.008 · Cited by 430
DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice
Vermulst, M., Wanagat, J., Kujoth, G. C., Bielas, J. H., Rabinovitch, P. S., Prolla, T. A., & Loeb, L. A. (2008) · Nature Genetics · doi:10.1038/ng.95 · Cited by 411
PTEN-deficient intestinal stem cells initiate intestinal polyposis
He, X. C., Yin, T., Grindley, J. C., Tian, Q., Sato, T., Tao, W. A., Dirisina, R., Porter-Westpfahl, K. S., Hembree, M., Johnson, T., et al. (2007) · Nature Genetics · doi:10.1038/ng1928 · Cited by 417
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Metadata
- Authors
- Greaves, L. C., Preston, S. L., Tadrous, P. J., Taylor, R. W., Barron, M. J., Oukrif, D., Leedham, S. J., Deheragoda, M., Sasieni, P., Novelli, M. R., Jankowski, J. A. Z., Turnbull, D. M., Wright, N. A., & McDonald, S. A. C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-01-06
- Volume
- 103
- Issue
- 3
- Pages
- 714-719
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2152660706
- Cited by
- 293
- References
- 26
- FWCI
- 16.25
- Type
- journal article
- Language
- en
- Open access
- green
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- Greaves, L. C., Preston, S. L., Tadrous, P. J., Taylor, R. W., Barron, M. J., Oukrif, D., Leedham, S. J., Deheragoda, M., Sasieni, P., Novelli, M. R., Jankowski, J. A. Z., Turnbull, D. M., Wright, N. A., & McDonald, S. A. C. (2006). Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0505903103
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