A Mutator Phenotype in Cancer

Perspectives in Cancer Research

A Mutator Phenotype in Cancer¹

Lawrence A. Loeb²

Departments of Pathology and Biochemistry, The Joseph Gottstein Memorial Cancer Research Laboratory, University of Washington, Seattle, Washington 98195-7705

ABSTRACT

We have proposed that an early step in tumor progression isthe expression of a mutator phenotype resulting from mutationsin genes that normally function in the maintenance of geneticstability. There is new and strong experimental evidence thatsupports the concept of a mutator phenotype in cancer. As technologiesfor chromosomal visualization and DNA advance, there are increasingdata that human cancer cells contain large numbers of mutations.First, I will review the concept of a mutator phenotype. Second,I will present the recent evidence that individual cancer cellscontain thousands of mutations. Third, I will explore potentialtarget genes that are required for maintenance of genetic stabilityin normal cells and ask if they are mutated in cancer cells.Fourth, I will address the timing of a mutator phenotype; isit an early event during tumor progression? Do tumors alreadycontain cells that harbor mutations rendering them resistantto most chemotherapeutic agents? Lastly, I will speculate onthe theoretical and practical implication of a mutator phenotypein cancer and consider the possibility of cancer preventionby delay, i.e., a reduction in mutation rates early during carcinogenesismight slow the progression of tumors.

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[Abstract] [Full Text] [PDF]

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[Abstract] [PDF]

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[Abstract] [Full Text] [PDF]

S. D. McCulloch, L. Gu, and G.-M. Li
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J. Biol. Chem., December 12, 2003; 278(50): 50803 - 50809.
[Abstract] [Full Text] [PDF]

M. A. Nowak, F. Michor, and Y. Iwasa
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[Abstract] [Full Text] [PDF]

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Mutagenesis, November 1, 2003; 18(6): 521 - 525.
[Abstract] [Full Text] [PDF]

R.-A. Risques, V. Moreno, M. Ribas, E. Marcuello, G. Capella, and M. A. Peinado
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Cancer Res., November 1, 2003; 63(21): 7206 - 7214.
[Abstract] [Full Text] [PDF]

N. L. Komarova and D. Wodarz
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Cancer Res., October 15, 2003; 63(20): 6635 - 6642.
[Abstract] [Full Text] [PDF]

R. A. Gatenby and T. L. Vincent
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Cancer Res., October 1, 2003; 63(19): 6212 - 6220.
[Abstract] [Full Text] [PDF]

A. N. Carnell and J. I. Goodman
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Toxicol. Sci., October 1, 2003; 75(2): 229 - 235.
[Abstract] [Full Text] [PDF]

A. L. Sabichi, M.-F. Demierre, E. T. Hawk, C. E. Lerman, and S. M. Lippman
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Cancer Res., September 15, 2003; 63(18): 5649 - 5655.
[Full Text] [PDF]

J. Z. Chen, N. Gokden, G. F. Greene, B. Green, and F. F. Kadlubar
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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

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[Full Text] [PDF]

Y.-P. Fu, J.-C. Yu, T.-C. Cheng, M. A. Lou, G.-C. Hsu, C.-Y. Wu, S.-T. Chen, H.-S. Wu, P.-E. Wu, and C.-Y. Shen
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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

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Clin. Cancer Res., March 1, 2003; 9(3): 1057 - 1062.
[Abstract] [Full Text] [PDF]

P. V. Shcherbakova, K. Bebenek, and T. A. Kunkel
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T.-L. Tseng, Y.-P. Shih, Y.-C. Huang, C.-K. Wang, P.-H. Chen, J.-G. Chang, K.-T. Yeh, Y.-M. A. Chen, and K. H. Buetow
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A. Hartmann, L. Zanardo, T. Bocker-Edmonston, H. Blaszyk, W. Dietmaier, R. Stoehr, J. C. Cheville, K. Junker, W. Wieland, R. Knuechel, et al.
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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

R. E. Goldsby, L. E. Hays, X. Chen, E. A. Olmsted, W. B. Slayton, G. J. Spangrude, and B. D. Preston
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PNAS, November 26, 2002; 99(24): 15560 - 15565.
[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

Y. Nie, J. Liao, X. Zhao, Y. Song, G.-y. Yang, L.-D. Wang, and C. S. Yang
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[Abstract] [Full Text] [PDF]

S. M. Lippman and W. K. Hong
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Cancer Res., September 15, 2002; 62(18): 5119 - 5125.
[Full Text] [PDF]

D.-S. Yoon, R. P. Wersto, W. Zhou, F. J. Chrest, E. S. Garrett, T. K. Kwon, and E. Gabrielson
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Am. J. Pathol., August 1, 2002; 161(2): 391 - 397.
[Abstract] [Full Text] [PDF]

S. A. Kuismanen, A.-L. Moisio, P. Schweizer, K. Truninger, R. Salovaara, J. Arola, R. Butzow, J. Jiricny, M. Nystrom-Lahti, and P. Peltomaki
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[Abstract] [Full Text] [PDF]

J.-G. Chen and S. B. Horwitz
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Cancer Res., April 1, 2002; 62(7): 1935 - 1938.
[Abstract] [Full Text] [PDF]

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Am. J. Pathol., April 1, 2002; 160(4): 1503 - 1506.
[Abstract] [Full Text] [PDF]

I. Tomlinson, P. Sasieni, and W. Bodmer
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Am. J. Pathol., March 1, 2002; 160(3): 755 - 758.
[Full Text] [PDF]

T.-L. Wang, C. Rago, N. Silliman, J. Ptak, S. Markowitz, J. K. V. Willson, G. Parmigiani, K. W. Kinzler, B. Vogelstein, and V. E. Velculescu
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PNAS, February 20, 2002; (2002) 261714699.
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J. Biol. Chem., December 7, 2001; 276(50): 46759 - 46764.
[Abstract] [Full Text] [PDF]

P. A. Egner, J.-B. Wang, Y.-R. Zhu, B.-C. Zhang, Y. Wu, Q.-N. Zhang, G.-S. Qian, S.-Y. Kuang, S. J. Gange, L. P. Jacobson, et al.
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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

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The Selection for Mismatch Repair Defects in Hereditary Nonpolyposis Colorectal Cancer: Revising the Mutator Hypothesis
Cancer Res., October 1, 2001; 61(20): 7369 - 7374.
[Full Text] [PDF]

M. Hanausek, P. Ganesh, Z. Walaszek, C. J. Arntzen, T. J. Slaga, and J. U. Gutterman
From the Cover: Avicins, a family of triterpenoid saponins from Acacia victoriae (Bentham), suppress H-ras mutations and aneuploidy in a murine skin carcinogenesis model
PNAS, September 25, 2001; 98(20): 11551 - 11556.
[Abstract] [Full Text] [PDF]

P. A. Egner, J.-B. Wang, Y.-R. Zhu, B.-C. Zhang, Y. Wu, Q.-N. Zhang, G.-S. Qian, S.-Y. Kuang, S. J. Gange, L. P. Jacobson, et al.
Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer
PNAS, December 4, 2001; 98(25): 14601 - 14606.
[Abstract] [Full Text] [PDF]

T.-L. Wang, C. Rago, N. Silliman, J. Ptak, S. Markowitz, J. K. V. Willson, G. Parmigiani, K. W. Kinzler, B. Vogelstein, and V. E. Velculescu
Prevalence of somatic alterations in the colorectal cancer cell genome
PNAS, March 5, 2002; 99(5): 3076 - 3080.
[Abstract] [Full Text] [PDF]