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

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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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Acknowledgments

Felix Sahm is a fellow of the Medical Faculty Heidelberg PostDoc-Program.

Author information

Authors and Affiliations

  1. Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany

    Christian Koelsche, Felix Sahm, David Capper, David Reuss, Katja Böhmer, Andrey Korshunov & Andreas von Deimling

  2. Clinical Cooperation Unit Neuropathology, German Cancer Research Center Heidelberg (DKFZ), INF 280, 69120, Heidelberg, Germany

    Christian Koelsche, Felix Sahm, David Capper, David Reuss, Jochen Meyer, Andrey Korshunov & Andreas von Deimling

  3. Department of Pediatric Oncology, Hematology and Immunology, Ruprecht-Karls-University Heidelberg, INF 430, 69120, Heidelberg, Germany

    Dominik Sturm & Stefan Pfister

  4. Division of Pediatric Neurooncology, German Cancer Research Center Heidelberg (DKFZ), INF 580, 69120, Heidelberg, Germany

    Dominik Sturm, David T. W. Jones, Marcel Kool, Paul A. Northcott & Stefan Pfister

  5. Department of Neurooncology, Neurology Clinic and National Center for Tumor Disease, University of Heidelberg and German Cancer Research Center, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Benedikt Wiestler, Michael Platten & Wolfgang Wick

  6. Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany

    Benedikt Wiestler & Wolfgang Wick

  7. Department of Neuropathology, Otto von Guericke University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany

    Christian Mawrin

  8. Department of Neuropathology, Institute of Pathology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Christian Hartmann

  9. Neurological Institute (Edinger-Institute), Goethe University, Heinrich-Hoffmann Str. 7, 60528, Frankfurt/Main, Germany

    Michel Mittelbronn

  10. German Cancer Consortium (DKTK) Heidelberg, Heidelberg, Germany

    Michel Mittelbronn

  11. Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149, Münster, Germany

    Benjamin Brokinkel

  12. Department of Neurosurgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    Marcel Seiz

  13. Department of Neurosurgery, University Hospital Heidelberg, 69120, Heidelberg, Germany

    Christel Herold-Mende & Andreas Unterberg

  14. Department of Neuropathology, Institute of Pathology and Neuropathology, University Tübingen, 72076, Tübingen, Germany

    Jens Schittenhelm

  15. Department of Neurology, University Hospital Zurich and Center for Neurosciences, University of Zurich, 8091, Zurich, Switzerland

    Michael Weller

  16. Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany

    Michael Platten

Authors
  1. Christian Koelsche
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  2. Felix Sahm
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  3. David Capper
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  4. David Reuss
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  5. Dominik Sturm
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  6. David T. W. Jones
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  7. Marcel Kool
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  8. Paul A. Northcott
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  9. Benedikt Wiestler
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  10. Katja Böhmer
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  11. Jochen Meyer
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  12. Christian Mawrin
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  13. Christian Hartmann
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  14. Michel Mittelbronn
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  15. Michael Platten
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  16. Benjamin Brokinkel
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  17. Marcel Seiz
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  18. Christel Herold-Mende
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  19. Andreas Unterberg
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  20. Jens Schittenhelm
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  21. Michael Weller
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  22. Stefan Pfister
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  23. Wolfgang Wick
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  24. Andrey Korshunov
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  25. Andreas von Deimling
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Corresponding author

Correspondence to Andreas von Deimling.

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Koelsche, C., Sahm, F., Capper, D. et al. Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system. Acta Neuropathol 126, 907–915 (2013). https://doi.org/10.1007/s00401-013-1195-5

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  • DOI: https://doi.org/10.1007/s00401-013-1195-5

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