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Author Notes:

Correspondence: Andreas von Deimling, Phone: +49-6221-564651, Fax: +49-6221-564566, Email: andreas.vondeimling@med.uni-heidelberg.de; Michael D. Taylor, Phone: +416-813-6427, Fax: +416-813-4975, Email: mdtaylor@sickkids.ca

We thank Susan Archer for technical writing, and Nick Downey from Integrated DNA Technologies for support with probe/primer design.

We acknowledge CRB HCL—Neurobiotec tumor bank (Hospices Civils de Lyon, Lyon, France).


Research Funding:

MDT is supported by a CIHR Clinician Scientist Phase II award, funds from the Garron Family Chair in Childhood Cancer Research at The Hospital for Sick Children and the University of Toronto, and operating funds from the Canadian Institutes of Health Research, the National Institutes of Health (R01CA159859 and R01CA148699) and the Pediatric Brain Tumor Foundation.

MR is supported by a fellowship from the Dr. Mildred Scheel Foundation for Cancer Research/German Cancer Aid and funds from the Baden-Wurttemberg Foundation.

VR is supported by a CIHR fellowship and an Alberta Innovates-Health Solutions Clinical Fellowship.

KZ acknowledges research support from MH CZ-DRO FNBr 65269705.

AK was supported by the TAMOP-4.2.2A-11/1/KONV-2012-0025 project and the János Bolyai Scholarship of the Hungarian Academy of Sciences.

The authors declare no conflicts of interest.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Neurosciences
  • Pathology
  • Neurosciences & Neurology
  • TERT promoter mutations
  • SHH pathway
  • Adult
  • Medulloblastoma

TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

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Journal Title:

Acta Neuropathologica


Volume 126, Number 6


, Pages 917-929

Type of Work:

Article | Final Publisher PDF


Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in < 5 % of cases and showed no association with increased patient age. The prognostic implications of these mutations were highly subgroup-specific. TERT mutations identified a subset with good and poor prognosis in SHH and Group 4 tumors, respectively. Monosomy 6 was mostly restricted to WNT tumors without TERT mutations. Hallmark SHH focal copy number aberrations and chromosome 10q deletion were mutually exclusive with TERT mutations within SHH tumors. TERT promoter mutations are the most common recurrent somatic point mutation in medulloblastoma, and are very highly enriched in adult SHH and WNT tumors. TERT mutations define a subset of SHH medulloblastoma with distinct demographics, cytogenetics, and outcomes.

Copyright information:

© Springer-Verlag Berlin Heidelberg 2013.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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