Article

Cancer progression by non-clonal chromosome aberrations.

Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Journal of Cellular Biochemistry (impact factor: 2.87). 09/2006; 98(6):1424-35. DOI:10.1002/jcb.20964 pp.1424-35
Source: PubMed

ABSTRACT The establishment of the correct conceptual framework is vital to any scientific discipline including cancer research. Influenced by hematologic cancer studies, the current cancer concept focuses on the stepwise patterns of progression as defined by specific recurrent genetic aberrations. This concept has faced a tough challenge as the majority of cancer cases follow non-linear patterns and display stochastic progression. In light of the recent discovery that genomic instability is directly linked to stochastic non-clonal chromosome aberrations (NCCAs), and that cancer progression can be characterized as a dynamic relationship between NCCAs and recurrent clonal chromosome aberrations (CCAs), we propose that the dynamics of NCCAs is a key element for karyotypic evolution in solid tumors. To support this viewpoint, we briefly discuss various basic elements responsible for cancer initiation and progression within an evolutionary context. We argue that even though stochastic changes can be detected at various levels of genetic organization, such as at the gene level and epigenetic level, it is primarily detected at the chromosomal or genome level. Thus, NCCA-mediated genomic variation plays a dominant role in cancer progression. To further illustrate the involvement of NCCA/CCA cycles in the pattern of cancer evolution, four cancer evolutionary models have been proposed based on the comparative analysis of karyotype patterns of various types of cancer.

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Keywords

cancer evolutionary models
 
cancer progression
 
correct conceptual framework
 
display stochastic progression
 
dynamic relationship
 
epigenetic level
 
gene level
 
genetic organization
 
genome level
 
karyotype patterns
 
key element
 
NCCA-mediated genomic variation
 
non-linear patterns
 
recent discovery
 
recurrent clonal chromosome aberrations
 
scientific discipline
 
solid tumors
 
stepwise patterns
 
various basic elements responsible
 
various types