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Mismatch Repair Deficiency in Phenotypically Normal Human Cells
Abstract
Tumor cells in patients with hereditary nonpolyposis colorectal cancer (HNPCC) are characterized by a genetic hypermutability caused by defects in DNA mismatch repair. A subset of HNPCC patients was found to have widespread mutations not only in their tumors, but also in their non-neoplastic cells. Although these patients had numerous mutations in all tissues examined, they had very few tumors. The hypermutability was associated with a profound defect in mismatch repair at the biochemical level. These results have implications for the relation between mutagenesis and carcinogenesis, and they suggest that mismatch repair deficiency is compatible with normal human development.
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Cited by
Lessons from hereditary colorectal cancer
Kinzler, K. W., & Vogelstein, B. (1996) · Cell · doi:10.1016/s0092-8674(00)81333-1 · Cited by 4,919
Self-citationDrake, J. W., Charlesworth, B., Charlesworth, D., & Crow, J. F. (1998) · Genetics · doi:10.1093/genetics/148.4.1667 · Cited by 1,932
Vogelstein, B., & Kinzler, K. W. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.16.9236 · Cited by 1,770
Self-citationBuermeyer, A. B., Deschênes, S. M., Baker, S. M., & Liskay, R. M. (1999) · Annual Review of Genetics · doi:10.1146/annurev.genet.33.1.533 · Cited by 451
The somatic mutation theory of cancer: growing problems with the paradigm?
Soto, A. M., & Sonnenschein, C. (2004) · BioEssays · doi:10.1002/bies.20087 · Cited by 295
Metadata
- Authors
- Parsons, R., Li, G.-M., Longley, M., Modrich, P., Liu, B., Berk, T., Hamilton, S. R., Kinzler, K. W., & Vogelstein, B.
- Venue
- Science
- Published
- 1995-05-05
- Volume
- 268
- Issue
- 5211
- Pages
- 738-740
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2036182319
- Cited by
- 305
- References
- 0
- FWCI
- 33.40
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Mismatch Repair Deficiency in Phenotypically Normal Human Cells. https://app.cochat.ai/papers/10.1126/science.7632227
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- Parsons, R., Li, G.-M., Longley, M., Modrich, P., Liu, B., Berk, T., Hamilton, S. R., Kinzler, K. W., & Vogelstein, B. (1995). Mismatch Repair Deficiency in Phenotypically Normal Human Cells. Science. https://doi.org/10.1126/science.7632227
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