The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Half or more of the somatic mutations in cancers of self-renewing tissues originate prior to tumor initiation
Open accessAbstract
Although it has been hypothesized that some of the somatic mutations found in tumors may occur before tumor initiation, there is little experimental or conceptual data on this topic. To gain insights into this fundamental issue, we formulated a mathematical model for the evolution of somatic mutations in which all relevant phases of a tissue’s history are considered. The model makes the prediction, validated by our empirical findings, that the number of somatic mutations in tumors of self-renewing tissues is positively correlated with the age of the patient at diagnosis. Importantly, our analysis indicates that half or more of the somatic mutations in certain tumors of self-renewing tissues occur before the onset of neoplasia. The model also provides a unique way to estimate the in vivo tissue-specific somatic mutation rates in normal tissues directly from the sequencing data of tumors. Our results have substantial implications for the interpretation of the large number of genome-wide cancer studies now being undertaken.
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Cites
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Self-citationStem Cells, Self-Renewal, and Differentiation in the Intestinal Epithelium
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Cited by
Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013) · Science · doi:10.1126/science.1235122 · Cited by 7,863
Self-citationClonal heterogeneity and tumor evolution: past, present, and the future
McGranahan, N., & Swanton, C. (2017) · Cell · doi:10.1016/j.cell.2017.01.018 · Cited by 2,840
Variation in cancer risk among tissues can be explained by the number of stem cell divisions
Tomasetti, C., & Vogelstein, B. (2015) · Science · doi:10.1126/science.1260825 · Cited by 1,927
Self-citationHigh burden and pervasive positive selection of somatic mutations in normal human skin
Martincorena, I., Roshan, A., Gerstung, M., Ellis, P., Van Loo, P., McLaren, S., Wedge, D. C., Fullam, A., Alexandrov, L. B., Tubio, J. M., et al. (2015) · Science · doi:10.1126/science.aaa6806 · Cited by 1,770
Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly
Zink, F., Stacey, S. N., Norddahl, G. L., Frigge, M. L., Magnusson, O. T., Jonsdottir, I., Thorgeirsson, T. E., Sigurdsson, A., Gudjonsson, S. A., Gudmundsson, J., et al. (2017) · Blood · doi:10.1182/blood-2017-02-769869 · Cited by 777
Metadata
- Authors
- Tomasetti, C., Vogelstein, B., & Parmigiani, G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2013-01-23
- Volume
- 110
- Issue
- 6
- Pages
- 1999-2004
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2086535578
- Cited by
- 414
- References
- 25
- FWCI
- 14.90
- Type
- journal article
- Language
- en
- Open access
- green
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- Tomasetti, C., Vogelstein, B., & Parmigiani, G. (2013). Half or more of the somatic mutations in cancers of self-renewing tissues originate prior to tumor initiation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1221068110
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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