title: Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system.
abstract: Hot spot mutations in the promoter region of telomerase reverse transcriptase (TERT) have recently been described in several human tumor entities. These mutations result in an upregulation of the telomerase complex activity and thus constitute a relevant mechanism for immortalization of tumor cells. Knowledge of the TERT promoter status in tumors is likely to be of interest for molecular classification and as a potential target for therapy. We, therefore, performed a systematic analysis of TERT promoter mutations in 1,515 tumors of the human nervous system and its coverings including 373 pediatric and 1,142 adult patients. We detected a total of 327 mutations. TERT promoter mutations were exceedingly rare in tumors typically encountered in pediatric patients. In entities typically encountered in adult patients TERT promoter mutations were strongly associated with older age (p < 0.0001). Highest mutation frequencies were detected in gliosarcomas (81 %), oligodendrogliomas (78 %), oligoastrocytomas (58 %), primary glioblastomas (54 %), and solitary fibrous tumors (50 %). Related to other molecular alterations, TERT promoter mutations were strongly associated with 1p/19q loss (p < 0.0001), but inversely associated with loss of ATRX expression (p < 0.0001) and IDH1/IDH2 mutations (p < 0.0001). TERT promoter mutations are typically found in adult patients and occur in a highly tumor type-associated distribution.
authors.affiliation: Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Koelsche
authors.forename: Felix
authors.initials: F
authors.lastname: Sahm
authors.forename: David
authors.initials: D
authors.lastname: Capper
authors.forename: David
authors.initials: D
authors.lastname: Reuss
authors.forename: Dominik
authors.initials: D
authors.lastname: Sturm
authors.forename: David T W
authors.initials: DT
authors.lastname: Jones
authors.forename: Marcel
authors.initials: M
authors.lastname: Kool
authors.forename: Paul A
authors.initials: PA
authors.lastname: Northcott
authors.forename: Benedikt
authors.initials: B
authors.lastname: Wiestler
authors.forename: Katja
authors.initials: K
authors.lastname: Böhmer
authors.forename: Jochen
authors.initials: J
authors.lastname: Meyer
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.forename: Christian
authors.initials: C
authors.lastname: Hartmann
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.forename: Michael
authors.initials: M
authors.lastname: Platten
authors.forename: Benjamin
authors.initials: B
authors.lastname: Brokinkel
authors.forename: Marcel
authors.initials: M
authors.lastname: Seiz
authors.forename: Christel
authors.initials: C
authors.lastname: Herold-Mende
authors.forename: Andreas
authors.initials: A
authors.lastname: Unterberg
authors.forename: Jens
authors.initials: J
authors.lastname: Schittenhelm
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.forename: Stefan
authors.initials: S
authors.lastname: Pfister
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
mesh_terms: D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics*
chemical_list: C509186:TERT protein, human; D019098:Telomerase