Abstract
The concept that cancers progress, in large part, through accumulation of multiple genetic abnormalities is generally accepted.1,2,3 The order of progression is best established for colorectal cancer.3 The development of genetic instability is thought to be a key aspect of tumor progression4,5 enabling accumulation of the multiple abnormalities required for a complete metastatic phenotype. Several genetic abnormalities that lead to instability have been identified. These involve genes that code for proteins involved in detection and repair of genetic damage,5 maintenance of telomere length6 and apoptosis.7,8 However, the magnitude and type of damage that is accumulated as a result of these defects is only now beginning to be appreciated. The application of molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH9,10) and comparative genomic hybridization (CGH11) are particularly powerful for the study of damage that results in changes in the structure or number of copies of genomic DNA. FISH allows visualization of specific segments of DNA in single cells and therefore provides information about the variation among cells in the number of copies and the organization of these target sequences. CGH, on the other hand provides a genome-wide overview of changes in relative DNA sequence copy number that occur in the majority of cells of a tumor. Importantly, CGH maps changes onto a normal representation of the genome so that they are easily interpreted. These techniques are particularly useful for studies of DNA sequence copy number changes in spontaneous solid tumors since they do not require cell culture and can be applied to archived tumor material.
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Gray, J.W., Chin, K., Waldman, F. (1997). A Molecular Cytogenetic View of Chromosomal Heterogeneity in Solid Tumors. In: Mihich, E., Hartwell, L. (eds) Genomic Instability and Immortality in Cancer. Pezcoller Foundation Symposia, vol 8. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5365-6_2
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DOI: https://doi.org/10.1007/978-1-4615-5365-6_2
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