Chromosomes and chromosomal progression of malignant human gliomas: theoretical and practical implications

Abstract

We karyotyped 27 malignant human gliomas including 3 anaplastic astrocytomas (AA), 23 glioblastoma multiformes (GBM), and 1 gliosarcoma (GS) in direct preparation, short term culture, or both, and found that they could be grouped according to their karyotypic patterns. Six of these tumors (3 GBM) had normal stemlines or only lacked one sex chromosome (Group la). Two tumors (Group lb) lacked one sex chromosome but showed, in addition, numerical and structural deviations. Three tumors were near-tetraploid (Group II) and contained double minutes (DMs). The remaining 16 tumors (I AA, 14 GBM, 1 GS) had near-diploid stemlines (Group III), often with gains of No. 7, loss of No. 10, structural abnormalities of No. 9 and DMs. These different patterns could be reflecting activation and/or amplification of different oncogenes. Alternatively they could be reflecting induction by different agents. But quite apart from their theoretical significance these karyotypic patterns could prove useful as prognostic indicators. The observa-tion that near-diploid human gliomas double their chromosome complements as they establish in culture and as transplantable lines in nude mice suggests that the near-tetraploid tumors in Group II are at a later stage of karyotypic progression than the near-diploid tumors in Groups I and III. There is also a spectrum of stage of karyotypic progression within Groups I and III ranging from tumors with only simple numerical deviations to those with complex numerical and structural abberations. The present series is too small and therapeutic regimens of individual patients are too diverse to determine if stage of karyotypic progression is a useful prognostic indicator. Long term studies of a large group of patients will be necessary to define these relationships.