Patterns of cellular proliferation in normal and tumor cell populations

Three types of cell mosaics have been used in mammalian studies: hemopoietic shimeras, mosaics formed by aggregation of preimplatation embryos, and mosaics resulting from X-chromosome inactivation. The problems investigated with these cell mosaics have included normal tissue orgaization, cell selection, primordial cell pool sizes, and tumor cell kinetics. The emphasis in this review is on the application of X-chromosome inactivation mosaics to the analysis of tumor cell proliferation. The first application of mosaicism to tumor ontogeny involved leiomyomas and demonstrated single cell and independent origin of the tumors. Other tumor studies are reviewed including those of presumed multiple cell origin, especially those of hereditary origin and viral etiology. The concept of target size is invoked to explain these multiple cell origin tumors. The recent reports on the clonal nature of atherosclerotic plaques is also discussed. Emphasis is placed on resolving the relationship between the multiclonal underlying fatty streak and the clonal plaque in order to understand the implications of the clonal plaques.