title: The role of telomere maintenance in the spontaneous growth arrest of pediatric low-grade gliomas.
abstract: Spontaneous tumor regression of pediatric low-grade gliomas (PLGG). We speculated that lack of telomere maintenance is responsible for this behavior. We first looked for evidence of telomerase activity and alternative lengthening of telomeres (ALT) in 56 PLGG. Telomerase activity was observed in 0 of 11 PLGG, in contrast to 10 of 13 high-grade pediatric brain tumors. There was no ALT in 45 of 45 samples. We then applied Q-FISH to eight patients whose indolent PLGG underwent two metachronous biopsies over a lag of several years. Telomere shortening was observed in the second biopsy in all tumors, but not in normal brain control (P < .0001), indicating that lack of telomere maintenance is associated with continuous telomere erosion. Based on these observations, we found that younger PLGG patients, who exhibit more aggressive and frequently recurrent tumors, had significantly longer telomeres than older ones (P = .00014). Tumors with a terminal restriction fragment length <7.5 did not recur, whereas the presence of longer telomeres (>8.0) conferred a high likelihood of late recurrences in PLGG. Our findings provide a plausible biologic mechanism to explain the tendency of PLGG to exhibit growth arrest and spontaneous regression. Telomere maintenance may therefore represent the first known biologic prognostic marker in PLGG.
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Uri
authors.initials: U
authors.lastname: Tabori
authors.forename: Bisera
authors.initials: B
authors.lastname: Vukovic
authors.forename: Maria
authors.initials: M
authors.lastname: Zielenska
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hawkins
authors.forename: Ilan
authors.initials: I
authors.lastname: Braude
authors.forename: James
authors.initials: J
authors.lastname: Rutka
authors.forename: Eric
authors.initials: E
authors.lastname: Bouffet
authors.forename: Jeremy
authors.initials: J
authors.lastname: Squire
authors.forename: David
authors.initials: D
authors.lastname: Malkin
mesh_terms: D001254:Astrocytoma / Q000235:genetics / Q000473:pathology; D001706:Biopsy; D001932:Brain Neoplasms / Q000473:pathology*; D002455:Cell Division; D002648:Child; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D004797:Enzyme-Linked Immunosorbent Assay; D004806:Ependymoma / Q000235:genetics / Q000473:pathology; D005910:Glioma / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009365:Neoplasm Regression, Spontaneous; D016133:Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000473:pathology / Q000502:physiology*
chemical_list: D004273:DNA, Neoplasm; D019098:Telomerase