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Journal of Neuro-Oncology

, Volume 141, Issue 1, pp 131–138 | Cite as

TERT promoter methylation is significantly associated with TERT upregulation and disease progression in pituitary adenomas

  • Yohei Miyake
  • Jun-ichi AdachiEmail author
  • Tomonari Suzuki
  • Kazuhiko Mishima
  • Ryuichiro Araki
  • Reina Mizuno
  • Ryo Nishikawa
Clinical Study

Abstract

Purpose

Alterations in the promoter of the telomerase reverse transcriptase (TERT) gene are a major mechanism of upregulating telomerase, which plays a crucial role in tumor development. Mutations in the TERT promoter have been observed in a subset of brain tumors, including adult gliomas and high-grade meningiomas. In pituitary adenomas (PAs), however, abnormalities in TERT are not fully understood. The present study aimed to investigate not only mutational but also methylation changes in the TERT promoter in PAs and to analyze their correlations with clinical variables.

Methods

We retrospectively studied 70 PAs consisting of 53 primary and 17 recurrent samples. Clinical data, including age at surgery, sex, largest tumor dimension, tumor subtype, resection rate, and progression-free survival (PFS), were obtained from medical records. We investigated TERT promoter hotspot mutations via Sanger sequencing and quantified the methylation status of the TERT promoter using methylation-sensitive high-resolution melting analysis (MS-HRM). Additionally, we investigated TERT mRNA expression using real-time quantitative PCR.

Results

TERT promoter hotspot mutations were not observed in any PA sample, while 16% of PAs exhibited TERT promoter methylation. PAs with methylated TERT promoters were significantly more likely to show disease progression, shorter PFS, and higher TERT expression levels compared to those with unmethylated promoters.

Conclusions

This is the first study showing that TERT promoter methylation is associated with disease progression and shorter PFS as well as upregulated TERT expression in PAs. Our results suggest that TERT promoter methylation may be a potential biomarker for predicting tumor recurrence in PAs.

Keywords

Pituitary adenoma Recurrence TERT promoter methylation TERT upregulation 

Notes

Acknowledgements

This work was supported by a grant from the Hidaka Research Project and a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (JSPS KAKENHI Grant Number 15K10369), 2015–2017. We would like to thank Ms. Kozue Watanabe and Ms. Ayako Kubota for their technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neuro-Oncology/NeurosurgerySaitama Medical University International Medical CenterHidakaJapan
  2. 2.Community Health Science CenterSaitama Medical UniversityMoroyamaJapan

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