The subpopulations and isolated cell types of freshly resected high grade human gliomas: their influence on the tumor's evolution in vivo and behavior and therapy in vitro

Abstract

Human malignant gliomas are karyotypically heterogeneous, composed of many cellular populations and isolated cell types identifiable by cytogenetic techniques. The distributions of cell types vary in high grade tumors. Some tumors are primarily near-diploid (35-57 chromosomes per cell), while others are hyperdiploid with chromosome numbers ranging from 58 to several hundred chromosomes per cell. Regional studies of several tumors suggest that the heterogeneity is not random. Anatomically different regions result from the combination of cellular distribution and their evolution over time. The karyotypic pattern of gliomas also reflects the tumor's evolution from a relatively homogeneous population of near-diploid cells to the hyperdiploid tumor that is removed by the neurosurgeon. The in vitro studies also suggest that there are phenotypic correlates to the karyotypic pattern of the tumor cells. Hyperdiploid cells are unstable in culture, tend to grow rapidly with short doubling times, and are often sensitive to such chemotherapeutic agents as BCNU. In contrast, the near-diploid cells are more normal in appearance, are stable in culture, grow slowly with long doubling times, are more likely to be resistant to the nitrosoureas and ultimately are the 'stem' cells that repopulate the tumor mass.