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Presence of alternative lengthening of telomeres mechanism in patients with glioblastoma identifies a less aggressive tumor type with longer survival

Patients with glioblastoma (GBM) have variable clinical courses, but the factors that underlie this heterogeneity are not understood. To determine whether the presence of the telomerase-independent alternative lengthening of telomeres (ALTs) mechanism is a significant prognostic factor for survival,...

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Hauptverfasser: McDonald, Kerrie L. (VerfasserIn) , McDonnell, Julie (VerfasserIn) , Muntoni, Alessandra (VerfasserIn) , Henson, Jeremy D. (VerfasserIn) , Hegi, Monika E. (VerfasserIn) , Deimling, Andreas von (VerfasserIn) , Wheeler, Helen R. (VerfasserIn) , Cook, Ray J. (VerfasserIn) , Biggs, Michael T. (VerfasserIn) , Little, Nicholas S. (VerfasserIn) , Robinson, Bruce G. (VerfasserIn) , Reddel, Roger R. (VerfasserIn) , Royds, Janice A. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 01 July 2010
In: Journal of neuropathology and experimental neurology
Year: 2010, Jahrgang: 69, Heft: 7, Pages: 729-736
ISSN:1554-6578
DOI:10.1097/NEN.0b013e3181e576cf
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1097/NEN.0b013e3181e576cf
Volltext
Verfasserangaben:Kerrie L. McDonald, PhD, Julie McDonnell, BSc, Alessandra Muntoni, MD, PhD, Jeremy D. Henson, MD, PhD, Monika E. Hegi, PhD, Andreas von Deimling, MD, Helen R. Wheeler, MD, Ray J. Cook, MD, Michael T. Biggs, MD, Nicholas S. Little, MD, Bruce G. Robinson, MD, MSc, Roger R. Reddel, MD, PhD, and Janice A. Royds, PhD
Beschreibung
Zusammenfassung:Patients with glioblastoma (GBM) have variable clinical courses, but the factors that underlie this heterogeneity are not understood. To determine whether the presence of the telomerase-independent alternative lengthening of telomeres (ALTs) mechanism is a significant prognostic factor for survival, we performed a retrospective analysis of 573 GBM patients. The presence of ALT was identified in paraffin sections using a combination of immunofluorescence for promyelocytic leukemia body and telomere fluorescence in situ hybridization. Alternative lengthening of telomere was present in 15% of the GBM patients. Patients with ALT had longer survival that was independent of age, surgery, and other treatments. Mutations in isocitrate dehydrogenase (IDH1mut) 1 frequently accompanied ALT, and in the presence of both molecular events, there was significantly longer overall survival. These data suggest that most ALT+ tumors may be less aggressive proneural GBMs, and the better prognosis may relate to the set of genetic changes associated with this tumor subtype. Despite improved overall survival of patients treated with the addition of chemotherapy to radiotherapy and surgery, ALT and chemotherapy independently provided a survival advantage, but these factors were not found to be additive. These results suggest a critical need for developing new therapies to target these specific GBM subtypes.
Beschreibung:Gesehen am 12.04.2023
Beschreibung:Online Resource
ISSN:1554-6578
DOI:10.1097/NEN.0b013e3181e576cf

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