Clinically distinct subgroups of glioblastoma multiforme studied by comparative genomic hybridization.

Studies investigating genetic alterations potentially constituting prognostic factors in glioblastoma multiforme (GBM) have centered mainly around amplification events. Comparative genomic hybridization (CGH) is a recent molecular cytogenetic technique that allows the detection of chromosomal imbalances and amplification sites in tumor DNA prepared from fresh or archival material. A group of 94 patients with GBM underwent surgery followed by a standard course of radiotherapy. Neuroradiologic monitoring with gadolinium-enhanced serial magnetic resonance imaging was applied to study the radiologically progression-free interval (RPFI) and tumor regrowth velocity. These parameters provided a clinical estimate of the postoperative tumor regrowth kinetics and yielded two clinically distinct groups. The most pronounced cases were selected from each group, i.e., those with the most favorable and unfavorable prognosis. Two subgroups with a statistically significant difference in RPFI (p < 0.001, Mann-Whitney U test) containing 10 patients each were formed: Subgroup A (slow tumor regrowth kinetics) and subgroup B (fast tumor regrowth kinetics). For a search of chromosomal alterations that might be correlated with tumor regrowth kinetics, we applied CGH to formalin-fixed, paraffin-embedded tumor tissue from these 20 patients. Except for autosomes 18 and 21, all chromosomes were involved at least once in copy-number aberrations. Events commonly associated with GBM, i.e., gains of chromosome 7, complete and partial losses of 9p, 10, and 22q, were not distributed differently between the two subgroups. The following differences were noticeable. Gains (including amplifications) of 12q14-q21 and of 19 were observed more often in subgroup A. Losses of 6q16-qter and parts of 13, and gains of 20, were more frequent in subgroup B. RPFI was significantly shorter for patients without amplification sites than for patients with gene amplification. RPFI did not differ significantly between patients with or without 7p12 amplification, where the epidermal growth factor receptor gene is localized. New amplification sites for GEM tumors were revealed at 11q13 and 11q22-q23. Loss of chromosome 10 was restricted to bands 10q25-q26 in one case. Although differences in the copy-number karyotypes of patients with slow and fast postoperative tumor-regrowth kinetics were noted, the present CGH study did not reveal any single alteration useful as a prognostic factor. In particular, these data do not support the assumption that patients suffering from GBM with amplification events would have a poorer prognosis than others.