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Cancer-predisposing genes and chromosome mutation

Some of human monogenic syndromes associated with high cancer propensity are characterized by an inherent tendency toward chromosome instability and provide an important key to the understanding of genetic control mechanism of chromosome mutation and its relevance to the development of neoplasms. Among those of recessive traits, some are unequivocally demonstrated to be associated with defects in DNA metabolism, which might be an integral component of the chromosome instability and cancer proneness of these diseases. However, in these diseases, the relationship between inherent genes and the development of cancer is rather indirect, and the gene traits do not provide sufficient information on the nature of mutation toward cancer. There is another class of genetic diseases, in which inherent gene for cancer proneness is expressed dominantly. They are not identified as an alteration in metabolism, but are more informative about the nature of the mutation toward cancer. In some of these diseases, the inherent genes promote chromosome structural rearrangements in their somatic cells. Such enhancement of chromosome mutation has been found in skin fibroblasts from patients with hereditary adenomatosis of colon, dominantly inherited familial childhood leukemia, familial colon cancer and prokeratosis of Mibelli.

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