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Journal of Neuro-Oncology

Published in:

01-01-2019 | Clinical Study

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

Authors: Yohei Miyake, Jun-ichi Adachi, Tomonari Suzuki, Kazuhiko Mishima, Ryuichiro Araki, Reina Mizuno, Ryo Nishikawa

Published in: Journal of Neuro-Oncology | Issue 1/2019

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.

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Title: TERT promoter methylation is significantly associated with TERT upregulation and disease progression in pituitary adenomas
Authors: Yohei Miyake
Jun-ichi Adachi
Tomonari Suzuki
Kazuhiko Mishima
Ryuichiro Araki
Reina Mizuno
Ryo Nishikawa
Publication date: 01-01-2019
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2019
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-018-03016-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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