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Acta Neuropathologica

, Volume 126, Issue 6, pp 907–915 | Cite as

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

  • 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 DeimlingEmail author
Original Paper

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.

Keywords

Astrocytoma Oligodendroglioma Glioblastoma Meningioma Medulloblastoma Brain tumor Pediatric TERT Promoter Mutation 

Notes

Acknowledgments

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

Supplementary material

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Christian Koelsche
    • 1
    • 2
  • Felix Sahm
    • 1
    • 2
  • David Capper
    • 1
    • 2
  • David Reuss
    • 1
    • 2
  • Dominik Sturm
    • 3
    • 4
  • David T. W. Jones
    • 4
  • Marcel Kool
    • 4
  • Paul A. Northcott
    • 4
  • Benedikt Wiestler
    • 5
    • 6
  • Katja Böhmer
    • 1
  • Jochen Meyer
    • 2
  • Christian Mawrin
    • 7
  • Christian Hartmann
    • 8
  • Michel Mittelbronn
    • 9
    • 10
  • Michael Platten
    • 5
    • 16
  • Benjamin Brokinkel
    • 11
  • Marcel Seiz
    • 12
  • Christel Herold-Mende
    • 13
  • Andreas Unterberg
    • 13
  • Jens Schittenhelm
    • 14
  • Michael Weller
    • 15
  • Stefan Pfister
    • 3
    • 4
  • Wolfgang Wick
    • 5
    • 6
  • Andrey Korshunov
    • 1
    • 2
  • Andreas von Deimling
    • 1
    • 2
    Email author
  1. 1.Department of Neuropathology, Institute of PathologyRuprecht-Karls-University HeidelbergHeidelbergGermany
  2. 2.Clinical Cooperation Unit NeuropathologyGerman Cancer Research Center Heidelberg (DKFZ)HeidelbergGermany
  3. 3.Department of Pediatric Oncology, Hematology and ImmunologyRuprecht-Karls-University HeidelbergHeidelbergGermany
  4. 4.Division of Pediatric NeurooncologyGerman Cancer Research Center Heidelberg (DKFZ)HeidelbergGermany
  5. 5.Department of Neurooncology, Neurology Clinic and National Center for Tumor DiseaseUniversity of Heidelberg and German Cancer Research CenterHeidelbergGermany
  6. 6.Clinical Cooperation Unit NeurooncologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  7. 7.Department of NeuropathologyOtto von Guericke University MagdeburgMagdeburgGermany
  8. 8.Department of Neuropathology, Institute of PathologyMedizinische Hochschule HannoverHannoverGermany
  9. 9.Neurological Institute (Edinger-Institute)Goethe UniversityFrankfurt/MainGermany
  10. 10.German Cancer Consortium (DKTK) HeidelbergHeidelbergGermany
  11. 11.Institute of NeuropathologyUniversity Hospital MünsterMünsterGermany
  12. 12.Department of Neurosurgery, University Medical Center Mannheim, Medical Faculty MannheimHeidelberg UniversityMannheimGermany
  13. 13.Department of NeurosurgeryUniversity Hospital HeidelbergHeidelbergGermany
  14. 14.Department of Neuropathology, Institute of Pathology and NeuropathologyUniversity TübingenTübingenGermany
  15. 15.Department of Neurology, University Hospital Zurich and Center for NeurosciencesUniversity of ZurichZurichSwitzerland
  16. 16.Clinical Cooperation Unit Neuroimmunology and Brain Tumor ImmunologyGerman Cancer Research Center (DKFZ)HeidelbergGermany

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