Carcinogenesis Advance Access published online on June 3, 2004
Carcinogenesis, doi:10.1093/carcin/bgh204
© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430
* To whom correspondence should be addressed. E-mail: brandt.schneider{at}ttmc.ttuhsc.edu.
Classical theories of carcinogenesis postulate that the accumulation of several somatic mutations is responsible for oncogenesis. However, these models do not explain how non-mutagenic carcinogens cause cancer. In addition, known mutation rates appear to be insufficient to account for observed cancer rates. Moreover, the current theory doesn't easily account for the long latencies observed in human cancers. Proponents of an aneuploidy-driven theory of carcinogenesis suggest that genomic instability has a causative role in carcinogenesis. In support of this theory, pre-neoplastic cells frequently display genomic instability while normal cells do not. Data obtained from a variety of model organisms have revealed that disruption of the cell cycle controls required for homeostasis results in the acquisition of genomic instability. Subsequently, this genomic instability becomes self-propagating via ‘destructive cycles’ and provides a medium for cellular selection and adaptation. Genomic instability allows numerous genetic and epigenetic alterations to accumulate during carcinogenesis without markedly changing phenotype until they are qualitatively or quantitatively sufficient to be selectively advantageous in the tumor microenvironment. Observations of adaptation in tumor cell populations and application of chaos theory may help elucidate the mechanism that drives the enormous genetic heterogeneity observed in tumors and provide insights into the development of new therapeutic cancer interventions and treatments.
Revised May 25, 2004
Accepted May 27, 2004
CARCINOGENESIS
Destructive cycles: the role of genomic instability and adaptation in carcinogenesis
2 Departments of Dermatology and Cell & Developmental Biology, Oregon Health & Science, University, Portland, Oregon, OR 97239, USA
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Zhao and R. J. Epstein Programmed Genetic Instability: A Tumor-Permissive Mechanism for Maintaining the Evolvability of Higher Species through Methylation-Dependent Mutation of DNA Repair Genes in the Male Germ Line Mol. Biol. Evol., August 1, 2008; 25(8): 1737 - 1749. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mattiuzzo, M. Fiore, R. Ricordy, and F. Degrassi Aneuploidy-inducing capacity of two widely used pesticides Carcinogenesis, December 1, 2006; 27(12): 2511 - 2518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Donahue, Q. Lin, S. Cao, and H. E. Ruley Carcinogens induce genome-wide loss of heterozygosity in normal stem cells without persistent chromosomal instability PNAS, August 1, 2006; 103(31): 11642 - 11646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Liu, A. Vo, G. Liu, and W. L. McKeehan Distinct Structural Domains within C19ORF5 Support Association with Stabilized Microtubules and Mitochondrial Aggregation and Genome Destruction Cancer Res., May 15, 2005; 65(10): 4191 - 4201. [Abstract] [Full Text] [PDF]
|
|