HE TENDENCY OF MANY TUMORS, over time, to ac-T quire more aggressive characteristics and more malignant behavior has long been recognized, and termed "tumor progression." Foulds' pointed out that this phenomenon often develops in a stepwise fashion through qualitatively different stages. During the last several decades, chromosome studies of tumors, along with other approaches, have suggested that this clinical and biological progression results, at least in part, from the sequential appearance within the neoplasm of cellular subpopulations whose new characteristics reflect specific somatic genetic Thus, the hallmarks of tumor progression-acquisition of the capacity to invade and to metastasize, more rapid growth rate, loss of responsiveness to hormones, decreased antigenicity, acquisition of drug resistance, etc-may be attributed to changes in the genes that regulate these functions, allowing sublines of the original neoplastic clone to emerge as predominant under the selective pressures exerted within the body of the individual bearing the tumor. Obviously, other factors may also play a role in the clinical and biological evolution of individual tumors, but there is increasing evidence for the importance of sequential genetic alterations as a major force in tumor progression.
Chromosome studies have added in a variety of ways to our understanding of tumor biology, and different aspects have been considered elsewhere in these page^.^.^ In this brief discussion, I will only consider how cytogenetic data have contributed to this "clonal evolution" view of tumor progression, and particularly how, in recent years, such studies have helped in identifying genes involved in this process and the mechanisms by which their function may be importantly altered so as to contribute to tumor development. I will focus chiefly on hematopoietic tumors, where my own collaborative studies with Dr. Carlo Croce have been mainly concentrated, with limited reference to the less extensive studies on tumors of other organ systems.