Acta Neuropathologica

, Volume 126, Issue 6, pp 931–937 | Cite as

TERT promoter mutations in primary and secondary glioblastomas

  • Naosuke Nonoguchi
  • Takashi Ohta
  • Ji-Eun Oh
  • Young-Ho Kim
  • Paul Kleihues
  • Hiroko OhgakiEmail author
Original Paper


Telomerase reverse transcriptase (TERT) is up-regulated in a variety of human neoplasms. Mutations in the core promoter region of the TERT gene, which increases promoter activity, have been reported in melanomas and a variety of human neoplasms, including gliomas. In the present study, we screened for TERT promoter mutations by direct DNA sequencing in a population-based collection of 358 glioblastomas. TERT promoter mutations (C228T, C250T) were detected in 55 % glioblastomas analysed. Of these, 73 % had a C228T mutation, and 27 % had a C250T mutation; only one glioblastoma had both C228T and C250T mutations. TERT promoter mutations were significantly more frequent in primary (IDH1 wild-type) glioblastomas (187/322; 58 %) than in secondary (IDH1 mutated) glioblastomas (10/36, 28 %; P = 0.0056). They showed significant inverse correlations with IDH1 mutations (P = 0.0056) and TP53 mutations (P = 0.043), and a significant positive correlation with EGFR amplification (P = 0.048). Glioblastoma patients with TERT mutations showed a shorter survival than those without TERT mutations in univariate analysis (median, 9.3 vs. 10.5 months; P = 0.015) and multivariate analysis after adjusting for age and gender (HR 1.38, 95 % CI 1.01–1.88, P = 0.041). However, TERT mutations had no significant impact on patients’ survival in multivariate analysis after further adjusting for other genetic alterations, or when primary and secondary glioblastomas were separately analysed. These results suggest that the prognostic value of TERT mutations for poor survival is largely due to their inverse correlation with IDH1 mutations, which are a significant prognostic marker of better survival in patients with secondary glioblastomas.


TERT promoter mutations IDH1 mutations Primary glioblastomas Secondary glioblastomas 

Supplementary material

401_2013_1163_MOESM1_ESM.ppt (1.1 mb)
Supplementary Fig. 1. Relationship between TERT promoter mutations, IDH1 mutations and 1p/19q co-deletion in all glioblastomas, primary glioblastomas, and secondary glioblastomas. Data are based on 200 cases for which all the data on TERT promoter mutations, IDH1 mutations and 1p/19q co-deletion are available. Supplementary Fig. 2. Multivariate analysis after adjusting for age, gender, and genetic alterations, showing that TERT promoter mutations are not prognostic for poor survival in glioblastomas. (PPT 1177 kb)
401_2013_1163_MOESM2_ESM.docx (20 kb)
Supplementary material (DOCX 20 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Naosuke Nonoguchi
    • 1
    • 2
  • Takashi Ohta
    • 1
  • Ji-Eun Oh
    • 1
  • Young-Ho Kim
    • 1
    • 3
  • Paul Kleihues
    • 4
  • Hiroko Ohgaki
    • 1
    Email author
  1. 1.Section of Molecular PathologyInternational Agency for Research on CancerLyonFrance
  2. 2.Department of NeurosurgeryOsaka Medical CollegeTakatsukiJapan
  3. 3.Translational Epidemiology Research BranchNational Cancer CenterGoyangKorea
  4. 4.Medical FacultyUniversity of ZurichZurichSwitzerland

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