CHROMOSOME FRAGILITY AND INSTABILITY IN HUMAN CANCER

The development of cancer is a multistep process triggered by physical, chemical, or biological carcinogenic factors, with the progression to an invasive phenotype requiring cumulative genetic alterations. Not all cellular genomic sequences are equally susceptible to carcinogenic factors or involved in pathologically relevant genetic alterations. Because of structural chromatin organization and DNA replication, certain genomic regions exhibit an increased fragility and tendency to recombination. At these regions, called fragile sites, there is a convergence of specific deletions, translocations, chemically induced lesions, and virus integrations. Isolation and cloning of sequences at fragile sites are important to a better understanding of the carcinogenesis process and to development of preventive measures.