Alternative lengthening of telomeres and survival in patients with glioblastoma multiforme

• Published in: The Lancet (British edition) Vol. 361; no. 9360; pp. 836 - 838
• Main Authors: Hakin-Smith, V, Jellinek, DA, Levy, D, Carroll, T, Teo, M, Timperley, WR, McKay, MJ, Reddel, RR, Royds, JA
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 08.03.2003; Lancet; Elsevier Limited
• Subjects: Adult; Age; Astrocytoma - enzymology; Astrocytoma - mortality; Astrocytoma - pathology; Biological and medical sciences; Cancer; Chromosomes; Data collection; Enzymes; Genotype & phenotype; Glioblastoma; Glioblastoma - enzymology; Glioblastoma - mortality; Glioblastoma - pathology; Humans; Medical prognosis; Medical research; Medical sciences; Middle Aged; Molecular chains; Mortality; Neurology; Pathogenesis; Patients; Phenotype; Prognosis; Radiation therapy; Regression analysis; Survival; Survival Analysis; Telomerase; Telomerase - metabolism; Telomere - genetics; Telomeres; Tumorigenesis; Tumors; Tumors of the nervous system. Phacomatoses; Writing; New Zealand; Malaysia; United Kingdom > UK; Australia; Human; Nervous system diseases; Prognosis; Enzyme; Age criterion; Biological marker; Malignant tumor; Glioblastoma multiforme; Telomere; Malignant glioma; Cox model; Enzymatic activity; Length; Cohort study; Central nervous system disease; Telomerase; Survival curve
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(03)12681-5

Despite advances in the molecular pathogenesis of glioblastoma multiforme, no reliable prognostic markers have been identified. We analysed telomerase activity and telomere lengths in glioblastoma multiformes from 77 patients. 19 patients (25%) had tumours with the alternative-lengthening-of-telomere (ALT) phenotype. Median survival for patients with this phenotype was 542 days (95% CI 114–970) compared with 247 days (224–270) for glioblastoma multiformes with normal telomeres (p=0·0003). Cox's regression analysis showed that this association is independent of age. In patients with non-ALT tumours, telomerase activity did not affect survival (median 287 [199–375] vs 236 [230–242] days, p=0·275). We conclude that ALT is a prognostic indicator for patients with glioblastoma multiforme.