The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Replication stress links structural and numerical cancer chromosomal instability
Abstract
Cancer chromosomal instability (CIN) results in an increased rate of change of chromosome number and structure and generates intratumour heterogeneity. CIN is observed in most solid tumours and is associated with both poor prognosis and drug resistance. Understanding a mechanistic basis for CIN is therefore paramount. Here we find evidence for impaired replication fork progression and increased DNA replication stress in CIN+ colorectal cancer (CRC) cells relative to CIN− CRC cells, with structural chromosome abnormalities precipitating chromosome missegregation in mitosis. We identify three new CIN-suppressor genes (PIGN (also known as MCD4), MEX3C (RKHD2) and ZNF516 (KIAA0222)) encoded on chromosome 18q that are subject to frequent copy number loss in CIN+ CRC. Chromosome 18q loss was temporally associated with aneuploidy onset at the adenoma–carcinoma transition. CIN-suppressor gene silencing leads to DNA replication stress, structural chromosome abnormalities and chromosome missegregation. Supplementing cells with nucleosides, to alleviate replication-associated damage, reduces the frequency of chromosome segregation errors after CIN-suppressor gene silencing, and attenuates segregation errors and DNA damage in CIN+ cells. These data implicate a central role for replication stress in the generation of structural and numerical CIN, which may inform new therapeutic approaches to limit intratumour heterogeneity.
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Self-citationGenetic instabilities in human cancers
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The causes and consequences of genetic heterogeneity in cancer evolution
Burrell, R. A., McGranahan, N., Bartek, J., & Swanton, C. (2013) · Nature · doi:10.1038/nature12625 · Cited by 2,262
Self-citationCauses and consequences of replication stress
Zeman, M. K., & Cimprich, K. A. (2014) · Nature Cell Biology · doi:10.1038/ncb2897 · Cited by 2,079
Chromosomal instability drives metastasis through a cytosolic DNA response
Bakhoum, S. F., Ngo, B., Laughney, A. M., Cavallo, J.-A., Murphy, C. J., Ly, P., Shah, P., Sriram, R. K., Watkins, T. B. K., Taunk, N. K., et al. (2018) · Nature · doi:10.1038/nature25432 · Cited by 1,593
Self-citationMatthews, H. K., Bertoli, C., & de Bruin, R. A. M. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00404-3 · Cited by 1,506
Biological and therapeutic impact of intratumor heterogeneity in cancer evolution
McGranahan, N., & Swanton, C. (2015) · Cancer Cell · doi:10.1016/j.ccell.2014.12.001 · Cited by 1,077
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Metadata
- Authors
- Burrell, R. A., McClelland, S. E., Endesfelder, D., Groth, P., Weller, M.-C., Shaikh, N., Domingo, E., Kanu, N., Dewhurst, S. M., Gronroos, E., Chew, S. K., Rowan, A. J., Schenk, A., Sheffer, M., Howell, M., Kschischo, M., Behrens, A., Helleday, T., Bartek, J., Tomlinson, I. P., & Swanton, C.
- Venue
- Nature
- Published
- 2013-02-27
- Volume
- 494
- Issue
- 7438
- Pages
- 492-496
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2084833108
- Cited by
- 878
- References
- 6
- FWCI
- 31.87
- Type
- journal article
- Language
- en
- Open access
- closed
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- Burrell, R. A., McClelland, S. E., Endesfelder, D., Groth, P., Weller, M.-C., Shaikh, N., Domingo, E., Kanu, N., Dewhurst, S. M., Gronroos, E., Chew, S. K., Rowan, A. J., Schenk, A., Sheffer, M., Howell, M., Kschischo, M., Behrens, A., Helleday, T., Bartek, J., . . . Swanton, C. (2013). Replication stress links structural and numerical cancer chromosomal instability. Nature. https://doi.org/10.1038/nature11935
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