In a continuing search for unique karyotypic changes in human leukemia and cancer, investigators have encountered a number of patients in whom partial trisomy and longitudinal duplication of some chromosomal regions, both involving especially the long arm of Chromosome 1, and isochromosomes were present. These abnormalities were also observed by us in human phytohemagglutinin-stimulated lymphocyte metaphases at the second mitosis following exposure to Mitomycin C, which induces a number of chromosome aberrations, i.e., breaks and exchanges. The occurrence of these abnormalities, i.e., partial trisomy and longitudinal duplication of chromosomes, could be attributed primarily to the manner of segregation of exchange quadriradials. The finding of isochromosomes at the second metaphase and the presence of adjacent-homologous exchanges at centromeric regions in the first metaphase after treatment with Mitomycin suggest the possibility of the production of isochromosomes through exchanges, as well as through “misdivision” of the centromere.

In addition to the possible mechanisms underlying the genesis of chromosome abnormalities mentioned above and frequently observed in human leukemia and cancer, a possible mechanism for the genesis of the Philadelphia chromosome is discussed on the basis of chromosomal findings in chronic myelocytic leukemia and changes induced by Mitomycin C.

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This study has been supported in part by Grants CA-14555 and CA-16935 from the National Cancer Institute. This is Paper 27 of the series “Chromosomes and Causation of Human Cancer and Leukemia.”

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