The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Differential DNA mismatch repair underlies mutation rate variation across the human genome
Open accessAbstract
Cancer genome sequencing has revealed considerable variation in somatic mutation rates across the human genome, with mutation rates elevated in heterochromatic late replicating regions and reduced in early replicating euchromatin. Multiple mechanisms have been suggested to underlie this, but the actual cause is unknown. Here we identify variable DNA mismatch repair (MMR) as the basis of this variation. Analysing ∼17 million single-nucleotide variants from the genomes of 652 tumours, we show that regional autosomal mutation rates at megabase resolution are largely stable across cancer types, with differences related to changes in replication timing and gene expression. However, mutations arising after the inactivation of MMR are no longer enriched in late replicating heterochromatin relative to early replicating euchromatin. Thus, differential DNA repair and not differential mutation supply is the primary cause of the large-scale regional mutation rate variation across the human genome.
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Chromatin organization is a major influence on regional mutation rates in human cancer cells
Schuster-Böckler, B., & Lehner, B. (2012) · Nature · doi:10.1038/nature11273 · Cited by 657 · cited 2×
“For the TS analysis, we considered those cell lines that (1) could be matched to a cancer type, based on their tissue of origin, and that (2) corresponded to one of the eight cancer types found to have a significant shift in PC3 of the regional mutation rates (Fig.”
MethodSelf-citation
Cited by
Endogenous DNA damage as a source of genomic instability in cancer
Tubbs, A., & Nussenzweig, A. (2017) · Cell · doi:10.1016/j.cell.2017.01.002 · Cited by 1,452
Somatic mutation in cancer and normal cells
Martincorena, I., & Campbell, P. J. (2015) · Science · doi:10.1126/science.aab4082 · Cited by 1,396
Classification and characterization of microsatellite instability across 18 cancer types
Hause, R. J., Pritchard, C. C., Shendure, J., & Salipante, S. J. (2016) · Nature Medicine · doi:10.1038/nm.4191 · Cited by 991
Tissue-specific mutation accumulation in human adult stem cells during life
Blokzijl, F., de Ligt, J., Jager, M., Sasselli, V., Roerink, S., Sasaki, N., Huch, M., Boymans, S., Kuijk, E., Prins, P., et al. (2016) · Nature · doi:10.1038/nature19768 · Cited by 935
Patterns of somatic structural variation in human cancer genomes
Li, Y., Roberts, N. D., Wala, J. A., Shapira, O., Schumacher, S. E., Kumar, K., Khurana, E., Waszak, S., Korbel, J. O., Haber, J. E., et al. (2020) · Nature · doi:10.1038/s41586-019-1913-9 · Cited by 867
Metadata
- Authors
- Supek, F., & Lehner, B.
- Venue
- Nature
- Published
- 2015-02-23
- Volume
- 521
- Issue
- 7550
- Pages
- 81-84
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2042793731
- Cited by
- 350
- References
- 9
- FWCI
- 12.56
- Type
- journal article
- Language
- en
- Open access
- green
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