&lt;i&gt;TERT&lt;/i&gt; promoter mutations in thyroid cancer

Matsuse, Michiko; Mitsutake, Norisato

doi:10.1507/endocrj.ej23-0136

Cited by 6 publications

(3 citation statements)

References 143 publications

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“…Molecular studies further revealed that the two mutations in TERT promoter generated consensus binding sites for ETS transcription factors and thereby promoted TERT activation (4,(35)(36)(37). A large number of genetic association studies have demonstrated that TERT promoter mutation is associated with multiple characteristics of aggressive tumor behaviors and patients with TERT promoter mutation had a higher risk of recurrence and mortality (12)(13)(14)(15)38).…”

Section: Discussionmentioning

confidence: 99%

TERT promoter methylation is associated with high expression of TERT and poor prognosis in papillary thyroid cancer

Li,

Xue,

Jiang

et al. 2024

Front. Oncol.

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The telomerase reverse transcriptase (TERT) is overexpressed and associated with poor prognosis in papillary thyroid cancer (PTC), the most common subtype of thyroid cancer. The overexpression of TERT in PTC was partially attributed to transcriptional activation by two hotspot mutations in the core promoter region of this gene. As one of the major epigenetic mechanisms of gene expression regulation, DNA methylation has been proved to regulate several tumor-related genes in PTC. However, the association of TERT promoter DNA methylation with TERT expression and PTC progression is still unclear. By treating PTC cell lines with demethylating agent decitabine, we found that the TERT promoter methylation and the genes’ expression were remarkably decreased. Consistently, PTC patients with TERT hypermethylation had significantly higher TERT expression than patients with TERT hypomethylation. Moreover, TERT hypermethylated patients showed significant higher rates of poor clinical outcomes than patients with TERT hypomethylation. Results from the cox regression analysis showed that the hazard ratios (HRs) of TERT hypermethylation for overall survival, disease-specific survival, disease-free interval (DFI) and progression-free interval (PFI) were 4.81 (95% CI, 1.61-14.41), 8.28 (95% CI, 2.14-32.13), 3.56 (95% CI, 1.24-10.17) and 3.32 (95% CI, 1.64-6.71), respectively. The HRs for DFI and PFI remained significant after adjustment for clinical risk factors. These data suggest that promoter DNA methylation upregulates TERT expression and associates with poor clinical outcomes of PTC, thus holds the potential to be a valuable prognostic marker for PTC risk stratification.

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Section: Discussionmentioning

confidence: 99%

TERT promoter methylation is associated with high expression of TERT and poor prognosis in papillary thyroid cancer

Li,

Xue,

Jiang

et al. 2024

Front. Oncol.

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“…TERT mutations are associated with older age (average 61.41 years) and a higher AF (average 46.71%). Research indicates that TERT mutation is infrequent in children and teenagers [ 22 ], while combined with BRAF mutation, they contribute to increased malignancy in thyroid cancer [ 23 , 24 ]. Our study suggested that TERT mutations are often accompanied by other mutations.…”

Section: Discussionmentioning

confidence: 99%

Genetic alterations and allele frequency of BRAF V600E and TERT mutation in papillary thyroid carcinoma with intermediate-to-high recurrence risk: a retrospective study

Huang,

Wang,

et al. 2024

Clin Exp Med

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The predictive value of allele frequency (AF) of BRAF V600E and TERT mutations in papillary thyroid carcinoma (PTC) remains controversial. We aimed to investigate the AF of BRAF V600E and TERT mutations in intermediate-to-high risk PTC and their association between tumor invasiveness, prognosis, and other mutations. Probe hybridization capture and high-throughput sequencing were used to quantitatively test 40 gene loci in 94 intermediate-to-high recurrence risk PTC patients, combined with clinical characteristics and follow-up for retrospective analysis. BRAF V600E mutation AF was linked to a increased risk of thyroid capsule penetration, recurrence, and concurrent mutations. Concurrent mutations could lead to a worse prognosis and increased invasiveness. TERT promoter mutation frequently accompanied other mutations and resulted in a poorer prognosis. However, there was no clear association between the TERT mutation AF and tumor invasiveness or recurrence. The sensitivity and specificity of predicting recurrence in intermediate-to-high risk PTC with BRAF V600E mutation AF > 28.2% were 60 and 80%. Although genetic alterations in PTC can differ among different ethnicities, the AF of BRAF V600E and TERT mutations may be similar. The AF of BRAF V600E has the potential to be a novel indicator in predicting PTC invasiveness and prognosis.

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“…TERT is not expressed in most human somatic cells; however, its expression and transcription are upregulated in many cancers through various mechanisms, including mutations in the core promoter region of the TERT gene. Moreover, it elongates telomeres, confers unlimited proliferative capacity to tumor cells, and contributes to tumor progression and aggressiveness [ 36 , 37 ]. Recently, it has been reported that TERT interacts with various signaling molecules such as NF-κ B, c-MYC, β-catenin, and TCF-4 to increase cancer malignancy and promote cancer progression [ 38 , 39 , 40 , 41 ].…”

Section: The Characteristics Of Atcmentioning

confidence: 99%

Recent Trends and Potential of Radiotherapy in the Treatment of Anaplastic Thyroid Cancer

Sekihara,

Himuro,

Toda

et al. 2024

Biomedicines

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Anaplastic thyroid cancer (ATC) is a rare but highly aggressive malignancy characterized by advanced disease at diagnosis and a poor prognosis. Despite multimodal therapeutic approaches that include surgery, radiotherapy, and chemotherapy, an optimal treatment strategy remains elusive. Current developments in targeted therapies and immunotherapy offer promising avenues for improved outcomes, particularly for BRAF-mutant patients. However, challenges remain regarding overcoming drug resistance and developing effective treatments for BRAF-wild-type tumors. This comprehensive review examines the clinical and biological features of ATC, outlines the current standards of care, and discusses recent developments with a focus on the evolving role of radiotherapy. Moreover, it emphasizes the necessity of a multidisciplinary approach and highlights the urgent need for further research to better understand ATC pathogenesis and identify new therapeutic targets. Collaborative efforts, including large-scale clinical trials, are essential for translating these findings into improved patient outcomes.

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<i>TERT</i> promoter mutations in thyroid cancer

Cited by 6 publications

References 143 publications

TERT promoter methylation is associated with high expression of TERT and poor prognosis in papillary thyroid cancer

TERT promoter methylation is associated with high expression of TERT and poor prognosis in papillary thyroid cancer

Genetic alterations and allele frequency of BRAF V600E and TERT mutation in papillary thyroid carcinoma with intermediate-to-high recurrence risk: a retrospective study

Recent Trends and Potential of Radiotherapy in the Treatment of Anaplastic Thyroid Cancer

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