Frequent mitotic errors in tumor cells of genetically micro-heterogeneous glioblastomas

Glioblastoma multiforme (GBM) is characterized by intratumoral heterogeneit y as to both histomorphology and genetic changes, displaying a wide variety of numerical chromosome aberrations the most common of which are monosomy 10 and trisomy 7. Moreover, GBM in vitro are known to have variable karyoty pes within a given tumor cell culture leading to rapid karyotype evolution through a high incidence of secondary numerical chromosome aberrations. The aim of our study was to investigate to what extent this mitotic instabilit y of glioblastoma cells is also present in vivo. We assessed the spatial di stribution patterns of numerical chromosome aberrations in vivo in a series of 24 GBM using two-color in situ hybridization for chromosomes 7/10, 8/17 , and 12/18 on consecutive 6-mum paraffin-embedded tissue slides. The chrom osome aberration patterns were compared with the histomorphology of the inv estigated tumor assessed from a consecutive HE-stained section, and with th e in vitro karyotype of cell cultures established from the tumors. All inve stigated chromosomes showed mitotic instability, i.e., numerical aberration s within significant amounts of tumor cells in a scattered distribution thr ough the tumor tissue. As to chromosomes 10 and 17, only monosomy occurred, as to chromosome 7 only trisomy/polysomy, apparently as a result of select ion in favor of the respective aberration. Conversely, chromosomes 8, 12, a nd 18 displayed scattered patterns of monosomy as well as trisomy within a given tumor reflecting a high mitotic error rate without selective effects. The karyotypes of the tumor cell cultures showed less variability of numer ical aberrations apparently due to clonal adaptation to in vitro conditions . We conclude that glioblastoma cells in vivo are characterized by an exten sive tendency to mitotic errors. The resulting clonal diversity of chromoso mally aberrant cells may be an important biological constituent of the well -known ability of glioblastomas to preserve viable tumor cell clones under adaptive stress in vivo, in clinical terms to rapidly recur after antitumor al therapy including radio- or chemotherapy. Copyright (C) 2001 S. Karger A G, Basel.