Abstract
In considering tumorigenesis, much attention is paid to genome instability and mutation rates. While reflecting on the circumstances that have led to this emphasis on mutation rates, Ian Tomlinson and Walter Bodmer point out that an increased mutation rate does not necessarily cause a tumor to grow and that selection is in fact the mechanism that drives the cellular, somatic evolution that leads to cancer.
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References
Brugarolas, J. & Jacks, T. Double indemnity: p53, BRCA and cancer. Nature Med. 3, 721–722 (1997).
Cairns, J. Mutation and cancer: the antecedents to our studies of adaptive mutation. Genetics 148, 1433–1440 (1998).
Kinzler, K.W. & Vogelstein, B.V. Lessons from hereditary colorectal cancer. Cell 87, 159–170 (1996).
Rotman, G. & Shiloh, Y. ATM: from gene to function. Hum. Mol. Genet. 7, 1555–1563 (1998).
Loeb, L.A., C.F. Springgate & Battula, N. Errors in DNA replication as a basis of malignant changes. Cancer Res. 34, 2311–2321 (1974).
Loeb, L.A. . Transient expression of a mutator phenotype in cancer cells. Science 277, 1449–1450 (1997).
Cairns, J. Mutation selection and the natural history of cancer. Nature 255, 197–200 (1975).
Tomlinson, I.P.M., M.R. Novelli & Bodmer, W.F. The mutation rate and cancer. Proc. Natl. Acad. Sci. USA 93, 14800–14803 (1996).
Homfray, T.F.R. et al. Defects in mismatch repair occur after APC mutations in the pathogenesis of sporadic colorectal tumors. Hum. Mutat. 11, 114–120 (1998).
Huang, J. et al. APC mutations in colorectal tumors with mismatch repair deficiency. Proc. Natl. Acad. Sci. USA 93, 9049–9054 (1996).
Nowell, P.C. The clonal evolution of tumor cell populations. Science 194, 23–28 (1976).
Orr–Weaver, T.L. & Weinberg, R.A. A checkpoint on the road to cancer. Nature 392, 223–224 (1998).
Loeb, L.A. Mutator phenotype may be required for multistage carcinogenesis. Cancer Res. 51, 3075–3079 (1991).
Tomlinson, I.P.M. & Bodmer, W.F. . Failure of programmed cell death and differentiation as causes of tumors: some simple mathematical models. Proc. Natl. Acad. Sci. USA 92, 11130–11134 (1995).
Richards, B. et al. Conditional mutator phenotypes in hMSH2–deficient tumor cell lines. Science 277, 1523–1525 (1997).
Branch, P. et al. Immune surveillance in colorectal carcinoma. Nature Genet. 9, 231–232 (1995).
Young, J. et al. Genomic instability occurs in colorectal carcinomas but not in adenomas. Hum. Mutat. 2, 351–354 (1993).
Davis, T.W. et al. Defective expression of the DNA mismatch repair protein, MLH1, alters G2–M cell cycle checkpoint arrest following ionizing radiation. Cancer Res. 58, 767–768 (1998).
Kinzler, K.W. & Vogelstein, B. Cancer–susceptibility genes. Gatekeepers and caretakers. Nature 386, 761–763 (1997).
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Tomlinson, I., Bodmer, W. Selection, the mutation rate and cancer: Ensuring that the tail does not wag the dog. Nat Med 5, 11–12 (1999). https://doi.org/10.1038/4687
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DOI: https://doi.org/10.1038/4687
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