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Review
. 2020 Sep;35(3):515-525.
doi: 10.3803/EnM.2020.304. Epub 2020 Sep 22.

Mechanisms of TERT Reactivation and Its Interaction with BRAFV600E

Young Shin Song  1 , Young Joo Park  2
Affiliations
Review

Mechanisms of TERT Reactivation and Its Interaction with BRAFV600E

Young Shin Song et al. Endocrinol Metab (Seoul). 2020 Sep.

Abstract

The telomerase reverse transcriptase (TERT) gene, which is repressed in most differentiated human cells, can be reactivated by somatic TERT alterations and epigenetic modulations. Moreover, the recruitment, accessibility, and binding of transcription factors also affect the regulation of TERT expression. Reactivated TERT contributes to the development and progression of cancer through telomere lengthening-dependent and independent ways. In particular, because of recent advances in high-throughput sequencing technologies, studies on genomic alterations in various cancers that cause increased TERT transcriptional activity have been actively conducted. TERT reactivation has been reported to be associated with poor prognosis in several cancers, and TERT promoter mutations are among the most potent prognostic markers in thyroid cancer. In particular, when a TERT promoter mutation coexists with the BRAFV600E mutation, these mutations exert synergistic effects on a poor prognosis. Efforts have been made to uncover the mechanisms of these synergistic interactions. In this review, we discuss the role of TERT reactivation in tumorigenesis, the mechanisms of TERT reactivation across all human cancers and in thyroid cancer, and the mechanisms of interactions between BRAFV600E and TERT promoter mutations.

Keywords: BRAF; Epigenomics; Genomics; Telomerase; Thyroid neoplasms.

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Conflict of interest statement

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1
Canonical and non-canonical functions of telomerase reverse transcriptase (TERT) in tumorigenesis. Telomerase/TERT reactivation causes cancer development and progression through telomere lengthening-dependent (canonical) and independent (non-canonical) mechanisms. NF-κB, nuclear factor-κB.
Fig. 2
Fig. 2
Mechanisms of telomerase reverse transcriptase (TERT) reactivation in cancer. TERT reactivation can occur by somatic TERT alterations (promoter mutation, amplification, and rearrangement) and epigenetic modulation (DNA methylation, non-coding RNA, and histone modification). WT, wild-type; MUT, mutant; ETS, E-twenty six.
Fig. 3
Fig. 3
Schematic representation of the mechanisms related to the causes and effects of how telomerase reverse transcriptase (TERT) reactivation leads to cancer development and progression.
See this image and copyright information in PMC

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