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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-12

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

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. More... »

PAGES

907-915

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00401-013-1195-5

    DOI

    http://dx.doi.org/10.1007/s00401-013-1195-5

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1025590471

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24154961


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