BACKGROUND: Glioblastoma multiforme (GBM) is a heterogeneous, highly aggressive 
primary brain tumor with strongly variable patient survival. Because reliable 
prognostic biomarkers are lacking, we investigated the relation between 
telomerase-associated parameters and the disease course.
METHODS: Telomerase-associated parameters were determined in 100 GBM tissues and 
associated with clinical characteristics and overall survival. Expressions of 
telomere length, telomerase activity (TA), and human telomerase reverse 
transcriptase (hTERT) were analyzed by quantitative PCR, telomeric repeat 
amplification protocol assay, and reverse transcriptase-PCR, respectively. 
Mutation status of isocitrate dehydrogenase (IDH)1 was determined by direct 
sequencing, and O(6)-methylguanine DNA methyltransferase (MGMT) promoter 
methylation by methylation-specific PCR.
RESULTS: Of 100 GBM tissues, 61 were positive for both hTERT mRNA and TA, with a 
highly significant correlation between both parameters (linear regression, P < 
.0001). Telomere length determination revealed a significant difference between 
the hTERT/TA-positive and -negative subgroups, with markedly longer telomeres in 
the hTERT/TA-negative cohort (unpaired Student's t-test, P = .0001). 
Accordingly, significantly shorter telomeres were detected in GBM tissues 
derived from older patients (>60 y at diagnosis, P < .0001). While no 
association of telomere parameters with MGMT promoter status was found, all 
tumors with IDH1 mutation (6/100) were negative for both hTERT expression and TA 
and harbored significantly longer telomeres. Patients with tumors lacking hTERT 
expression/TA showed a significant survival benefit (Kaplan-Meier test, both P < 
.01), which, however, was based exclusively on the younger patient subgroup (≤60 
y, both P < .005; >60 y, both ns).
CONCLUSIONS: Telomerase activation is not an independent prognostic parameter in 
GBM but predicts aggressive tumor behavior solely in a younger patient cohort.