title: Association of mutant TP53 with alternative lengthening of telomeres and favorable prognosis in glioma.
abstract: The molecular basis for alternative lengthening of telomeres (ALT), a prognostic marker for glioma patients, remains unknown. We examined TP53 status in relation to telomere maintenance mechanism (TMM) in 108 patients with glioblastoma multiforme and two patients with anaplastic astrocytoma from New Zealand and United Kingdom. Tumor samples were analyzed with respect to telomerase activity, telomere length, and ALT-associated promyelocytic leukemia nuclear bodies to determine their TMM. TP53 mutation was analyzed by direct sequencing of coding exons 2 to 11. We found an association between TP53 mutation and ALT mechanism and between wild-type TP53 and telomerase and absence of a known TMM (P < 0.0001). We suggest that TP53 deficiency plays a permissive role in the activation of ALT.
authors.affiliation: Department of Pathology, University of Otago, Dunedin, New Zealand.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
authors.forename: Vicky
authors.initials: V
authors.lastname: Hakin-Smith
authors.forename: Mario
authors.initials: M
authors.lastname: Teo
authors.forename: George E
authors.initials: GE
authors.lastname: Xinarianos
authors.forename: David A
authors.initials: DA
authors.lastname: Jellinek
authors.forename: Thomas
authors.initials: T
authors.lastname: Carroll
authors.forename: David
authors.initials: D
authors.lastname: McDowell
authors.forename: Martin R
authors.initials: MR
authors.lastname: MacFarlane
authors.forename: Ronald
authors.initials: R
authors.lastname: Boet
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Baguley
authors.forename: Antony W
authors.initials: AW
authors.lastname: Braithwaite
authors.forename: Roger R
authors.initials: RR
authors.lastname: Reddel
authors.forename: Janice A
authors.initials: JA
authors.lastname: Royds
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000235:genetics*; D005260:Female; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016615:Telomere / Q000235:genetics*