title: Prognostic significance of telomerase-associated parameters in glioblastoma: effect of patient age.
abstract: 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.
authors: Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090 Vienna, Austria.
authors: Daniela
authors: D
authors: Lötsch
authors: Bahil
authors: B
authors: Ghanim
authors: Magdalena
authors: M
authors: Laaber
authors: Gabriele
authors: G
authors: Wurm
authors: Serge
authors: S
authors: Weis
authors: Stefan
authors: S
authors: Lenz
authors: Gerald
authors: G
authors: Webersinke
authors: Josef
authors: J
authors: Pichler
authors: Walter
authors: W
authors: Berger
authors: Sabine
authors: S
authors: Spiegl-Kreinecker
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000201:enzymology / Q000401:mortality* / Q000628:therapy; D003131:Combined Modality Therapy; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000201:enzymology / Q000401:mortality* / Q000628:therapy; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C509186:TERT protein, human; D019098:Telomerase; D045643:DNA Repair Enzymes
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