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Genetic and phenotypic heterogeneity of human malignancies: finding order in chaos.

The presence of cellular heterogeneity within human tumors has been recognized for many years. Current concepts regarding the clonal origin of human neoplasms, and recent advances in the study of successive genetic changes that occur during tumor evolution may now make it possible to understand in greater depth the biological and clinical implications of intra-tumor heterogeneity at both the phenotypic and genotypic levels. In order to explore these concepts further, and to better identify the potential contributions that flow and image cytometry can make to our understanding of tumor heterogeneity, a session of the 1994 ISAC Congress was dedicated to plenary presentations on human cancer cell heterogeneity. Here, we provide a brief overview of the genetic evolutionary progression of human cancers, some considerations of clinically important phenotypic and genotypic markers, and an outline that might serve as a basis for framing relevant issues that are ammenable to further study. All Nature is but Art, unknown to thee; All Chance, Direction, which thou canst not see; All Discord, Harmony not understood: All partial Evil, universal Good. (Alexander Pope, Essay on Man, end of Epistle 1).