A Chromosomal Theory of Carcinogenesis

Abstract

Chromosome rearrangements that have been described in malignant processes are structural and numerical. Structural rearrangements produce marker chromosomes. The most remarkable instance is the Philadelphia chromosome (Ph1) present in chronic myelogenous leukemia. Other markers are known, but their specificity is not yet well established. Numerical changes may lead to complete karyotype upheaval. Yet, in favorable conditions—mostly during acute exacerbation of chronic myelogenous leukemia—numerical changes can be shown to represent systematic karyotypic evolutions. These clonal evolutions proceed according to certain patterns, and seven models have been proposed, depending on their degree of complexity. The mechanisms involved are acquisition and duplication of extra chromosomes, loss of chromosomes, acquisition of marker chromosomes, or a combination of different mechanisms. A general theory is discussed. Chromosome rearrangements would be the common pathway by which carcinogenic factors induce malignancy, with these factors being external: ionizing radiations, oncogenic viruses, carcinogenic chemicals, or internal, namely genetic diseases, gene mutations, immunological phenomena, and chromosome interaction.

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