The mutation rate and cancer.

The selection of advantageous mutations underlies tumorigenesis. The growth of a tumor is therefore a form of evolution at the somatic level, in which the population is comprised of individual cells within the tumor. Models of tumorigenesis have considered the relative importance of mutation and selection. We show that selection is more important than an increased mutation rate in the growth of a tumor. Some cancers may acquire a "mutator phenotype," probably leading to faster growth, but mutator phenotypes are not necessary for carcinogenesis.

[1]  M. Meuth,et al.  Mutator phenotypes in human colorectal carcinoma cell lines. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[2]  H. Koeffler,et al.  DNA aneuploidy in morphologically normal colons from patients with colon cancer. , 1995, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[3]  P. Karran.  Appropriate partners make good matches. , 1995, Science.

[4]  S H Moolgavkar,et al.  Mutation and cancer: a model for human carcinogenesis. , 1981, Journal of the National Cancer Institute.

[5]  P. Armitage,et al.  A Two-stage Theory of Carcinogenesis in Relation to the Age Distribution of Human Cancer , 1957, British Journal of Cancer.

[6]  F. Christians,et al.  Potential sources of multiple mutations in human cancers. , 1995, Preventive medicine.

[7]  C. Purdie,et al.  Stabilised p53 facilitates aneuploid clonal divergence in colorectal cancer. , 1993, Oncogene.

[8]  M. Lovett,et al.  A single ataxia telangiectasia gene with a product similar to PI-3 kinase. , 1995, Science.

[9]  D. Lane,et al.  p53, guardian of the genome , 1992, Nature.

[10]  A. Chapelle,et al.  Mismatch repair gene defects in sporadic colorectal cancers with microsatellite instability , 1995, Nature Genetics.

[11]  John Cairns,et al.  Mutation selection and the natural history of cancer , 1975, Nature.

[12]  B. Erdtmann,et al.  The effect of the pyrrolizidine alkaloid integerrimine on the chromosomes of mouse bone marrow cells. , 1990, Mutation research.

[13]  L. Loeb,et al.  Mutator phenotype may be required for multistage carcinogenesis. , 1991, Cancer research.

[14]  S. Moolgavkar.  Carcinogenesis modeling: from molecular biology to epidemiology. , 1986, Annual review of public health.

[15]  D. Spandidos,et al.  Microsatellite instability in human atherosclerotic plaques. , 1996, Biochemical and biophysical research communications.

[16]  D. Mitchell,et al.  Enhanced photoproduct repair: its role in the DNA damage-resistance phenotype of human malignant melanoma cells. , 1995, Cancer research.

[17]  W. Bodmer,et al.  Failure of programmed cell death and differentiation as causes of tumors: some simple mathematical models. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[18]  M. Lavin,et al.  Resistance of human melanoma cells to ultraviolet radiation. , 1976, Cancer research.

[19]  S. Broder,et al.  Molecular foundations of cancer: New targets for intervention , 1995, Nature Medicine.

[20]  G. Chenevix-Trench,et al.  Genomic instability occurs in colorectal carcinomas but not in adenomas , 1993, Human mutation.

[21]  D. Shibata,et al.  Genomic instability in repeated sequences is an early somatic event in colorectal tumorigenesis that persists after transformation , 1994, Nature Genetics.

[22]  A. Feinberg,et al.  Microallelotyping defines the sequence and tempo of alleiic losses at tumour suppressor gene loci during colorectal cancer progression , 1995, Nature Medicine.

[23]  J. C. FISHER,et al.  Multiple-Mutation Theory of Carcinogenesis , 1958, Nature.

[24]  M. Meuth,et al.  High rate of multilocus deletion in a human tumor cell line. , 1993, Human molecular genetics.