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Published in: Acta Neuropathologica 6/2013

01-12-2013 | Original Paper

Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system

Authors: Christian Koelsche, Felix Sahm, David Capper, David Reuss, Dominik Sturm, David T. W. Jones, Marcel Kool, Paul A. Northcott, Benedikt Wiestler, Katja Böhmer, Jochen Meyer, Christian Mawrin, Christian Hartmann, Michel Mittelbronn, Michael Platten, Benjamin Brokinkel, Marcel Seiz, Christel Herold-Mende, Andreas Unterberg, Jens Schittenhelm, Michael Weller, Stefan Pfister, Wolfgang Wick, Andrey Korshunov, Andreas von Deimling

Published in: Acta Neuropathologica | Issue 6/2013

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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.
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Metadata
Title
Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system
Authors
Christian Koelsche
Felix Sahm
David Capper
David Reuss
Dominik Sturm
David T. W. Jones
Marcel Kool
Paul A. Northcott
Benedikt Wiestler
Katja Böhmer
Jochen Meyer
Christian Mawrin
Christian Hartmann
Michel Mittelbronn
Michael Platten
Benjamin Brokinkel
Marcel Seiz
Christel Herold-Mende
Andreas Unterberg
Jens Schittenhelm
Michael Weller
Stefan Pfister
Wolfgang Wick
Andrey Korshunov
Andreas von Deimling
Publication date
01-12-2013
Publisher
Springer Berlin Heidelberg
Published in
Acta Neuropathologica / Issue 6/2013
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-013-1195-5

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