<i>TERT</i> mRNA Expression as a Novel Prognostic Marker in Papillary Thyroid Carcinomas

Tanaka, Aya; Matsuse, Michiko; Saenko, Vladimir; Nakao, Tomoe; Yamanouchi, Kaoru; Sakimura, Chika; Yano, Hiroshi; Nishihara, Eijun; Hirokawa, Mitsuyoshi; Suzuki, Keiji; Miyauchi, Akira; Eguchi, Susumu; Yoshiura, Ko–ichiro; Yamashita, Shunichi; Nagayasu, Takeshi; Mitsutake, Norisato

doi:10.1089/thy.2018.0695

Cited by 45 publications

(36 citation statements)

References 46 publications

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“…TERT mRNA expression has been proposed as a prognostic marker, independent of the TERT promoter mutation. A study in PTC found a subset of wildtype TERT tumors with high TERT expression, which correlated with a higher recurrence rate (70). However, other studies have shown that TERT immunohistochemistry (IHC), or measurement of protein expression is not a useful clinical tool for prognostication.…”

Section: Discussionmentioning

confidence: 99%

Telomerase Reverse Transcriptase (TERT) Regulation in Thyroid Cancer: A Review

2020

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Telomerase reverse transcriptase (TERT) is the catalytic subunit of the enzyme telomerase and is essential for telomerase activity. Upregulation of TERT expression and resulting telomerase activity occurs in the large majority of malignancies, including thyroid cancer. This upregulation results in continued cellular proliferation and avoidance of cellular senescence and cell death. In this review we will briefly introduce TERT and telomerase activity as it pertains to thyroid cancer and, highlight the effects of TERT on cancer cells. We will also explore in detail the different TERT regulatory strategies and how TERT is reactivated in thyroid cancer cells, specifically. These regulatory mechanisms include both activating single base pair TERT promoter mutations and epigenetic changes at the promoter, including changes in CpG methylation and histone modifications that affect chromatin structure. Further, regulation includes the allele-specific regulation of the TERT promoter in thyroid cancer cells harboring the TERT promoter mutation. These entail allele-specific transcriptional activator binding, DNA methylation, histone modifications, and mono-allelic expression of TERT. Lastly, TERT copy number alterations and alternative splicing are also implicated. Both amplifications of the TERT locus and increased full-length transcripts and decreased inactive and dominant negative isoforms result in active telomerase. Finally, the clinical significance of TERT in thyroid cancer is also reviewed.

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Section: Discussionmentioning

confidence: 99%

Telomerase Reverse Transcriptase (TERT) Regulation in Thyroid Cancer: A Review

2020

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“…TERT promoter mutations are well-known to be associated with high-risk clinicopathologic characteristics and poor outcomes of DTC [5,[34][35][36][37]. TERT expression has also been reported to be correlated with aggressive tumor behavior and a poorer prognosis in DTC, even independent of TERT promoter mutation status [67,[71][72][73].…”

Section: Mechanisms Of Tert Reactivation In Thyroid Cancermentioning

confidence: 99%

Mechanisms of TERT Reactivation and Its Interaction with BRAFV600E

Song¹,

Park²

2020

Endocrinol Metab

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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 BRAF V600E 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 BRAF V600E and TERT promoter mutations.

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“…They are known as effective risk factors for patients with PTC. Several investigators have shown that TERT promoter mutations are significantly more common among older patients, bigger tumor size, more aggressive subtype, tumors with extrathyroidal invasion, distant metastasis or higher stage at diagnosis, and are related to poor outcomes [7,[23][24][25][26][27][28]. In addition, Xing et al reported that coexisting BRAF V600E and TERT promoter mutations represented a strong predictor for the most aggressive PTCs with the highest recurrence rate [29].…”

Section: Discussionmentioning

confidence: 99%

TERT Promoter Mutation and Extent of Thyroidectomy in Patients with 1–4 cm Intrathyroidal Papillary Carcinoma

Ebina

Togashi

Baba

et al. 2020

Cancers

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There are concerns regarding overtreatment in papillary thyroid carcinoma (PTC). BRAF V600E and TERT promoter mutations play important roles in the development of PTC. However, initial surgical approaches for PTC based on genetic characteristics remain unclear. The present study aimed to identify genetic mutations as predictors of prognosis and to establish proper indications for lobectomy (LT) in patients with 1–4 cm intrathyroidal PTC. Prospectively accumulated data from 685 consecutive patients with PTC who underwent primary thyroid surgery at the Cancer Institute Hospital, Tokyo, Japan, between 2001 and 2012 were retrospectively reviewed. Of the 685 patients examined, 538 (78.5%) had BRAF V600E mutation and 133 (19.4%) had TERT promoter mutations. Patients with TERT promoter mutations displayed significantly worse outcomes than those without mutations (10-year cause-specific survival (CSS): 73.7% vs. 98.1%, p < 0.001; 10-year disease-free survival (DFS): 53.7% vs. 93.3%, p < 0.001). As for extent of thyroidectomy among TERT mutation-negative patients with 1–4 cm intrathyroidal PTC, patients who underwent LT showed no significant differences in 10-year CSS and 10-year DFS compared to patients who had total thyroidectomy (TT) under propensity score-matching. Avoiding TT for those patients indicates a possible pathway to prevent overtreatment and reduce postoperative complications.

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TERT mRNA Expression as a Novel Prognostic Marker in Papillary Thyroid Carcinomas

Cited by 45 publications

References 46 publications

Telomerase Reverse Transcriptase (TERT) Regulation in Thyroid Cancer: A Review

Telomerase Reverse Transcriptase (TERT) Regulation in Thyroid Cancer: A Review

Mechanisms of TERT Reactivation and Its Interaction with BRAFV600E

TERT Promoter Mutation and Extent of Thyroidectomy in Patients with 1–4 cm Intrathyroidal Papillary Carcinoma

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