Significance of chromosome change to hematopoietic neoplasms

The application of banding techniques to the study of tumor chromosomes during the past 10 yr has yielded extensive data defining the types of chromosome changes that occur in human hematopoietic and other tumors. Chromosome changes characterize most tumors and exhibit a high degree of nonrandomness; in some tumors, this nonrandomness is defined by the tumor-inducing agents, while in others, it is defined by target cells of tumorigenesis. These observations led to the suggestion that chromosome abnormalities impart a selective advantage to the cells in which they occur and hence are of importance in the development of tumors. The mechanisms by which cells carrying chromosome abnormalities gain selective advantage are beginning to become apparent as the recently acquired data on the molecular genetics of neoplastic transformation are considered in conjunction with cytogenetic data. Activation of cellular oncogenes and overproduction of their products has been shown to be a key step in some types of neoplastic transformation. Chromosome abnormality is suggested to accomplish this step by either causing alterations in oncogene dosage or by activating normally quiescent oncogenes by bringing them into the transcriptional control of active genes. The paradigm for the latter model is the development of human and murine B-cell neoplasms in which specific translocations transfer c-myc from its constitutive site to a site next to the immunoglobulin genes. The chromosomal positions of several oncogenes have now been determined, and the elucidation of their fate in association with chromosome abnormalities in tumor cells can be expected to clarify mechanisms of oncogenesis.