TERT Promoter Mutations Lead to High Transcriptional Activity under Hypoxia and Temozolomide Treatment and Predict Poor Prognosis in Gliomas

Chen, Chen; Han, Sheng; Meng, Lingxuan; Li, Zhonghua; Zhang, Xue; Wu, Anhua

doi:10.1371/journal.pone.0100297

Cited by 39 publications

(52 citation statements)

References 32 publications

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“…Telomerase reverse transcriptase (TErT), a catalytic subunit of telomerase that includes an rnA component (TErC), therewithal maintains the telomere homeostasis and chromosomal integrity (15). reactivation of TErT has been detected in approximately 90% of human cancers (3,(17)(18)(19)(20). This study attempted to investigate whether immunohistochemical expression of TErT differs in neoplastic and nonneoplastic pituitary tissues and aimed to investigate whether TErT expression is related to clinicopathological features of pituitary adenomas.…”

Section: Comparisons Of Cytoplasmic Tert Expression With Clinicopathomentioning

confidence: 99%

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Tert expression in pituitary adenomas

Can

Çelık²,

Bulbul³

et al. 2017

TJPATH

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Objective: Although pituitary adenomas have benign histomorphological features, some of them may present in an aggressive manner. To predict the behaviour of these tumours, telomerase reverse transcriptase (TErT) activity in pituitary adenomas has been the subject of a few studies with contradictory results. This study aims to investigate whether immunohistochemical expression of TErT differs in neoplastic and nonneoplastic pituitary tissues and aims to investigate whether TErT expression is related to clinicopathological features of pituitary adenomas. Material and Method:The study included 48 patients who had been diagnosed with pituitary adenomas and had clinical follow-ups. nonneoplastic pituitary tissues were obtained from autopsy specimens (n=20). Immunohistochemistry for TErT antibody was performed. Both the nuclear and cytoplasmic expression of TErT antibody was noted, and total combined TErT staining was evaluated according to nuclear and cytoplasmic stainings. Results:TErT expression did not differ between neoplastic and nonneoplastic pituitary tissues. neither total (combined nuclear and cytoplasmic) TErT nor nuclear TErT expression revealed any statistically significant relationship with any of the clinicopathological features. Higher cytoplasmic TErT expression was observed in adenomas with recurrence than adenomas without recurrence (p=0.035). Conclusion:This study introduces the notion that immunohistochemical expression of TErT does not differ in neoplastic and nonneoplastic pituitary tissues. Pituitary adenomas with cytoplasmic immunohistochemical expression of TErT have significantly higher rates of recurrence. Further studies, including combined methods of immunohistochemistry and molecular analyses in larger groups, may reveal applicable results for the clinical significance of TErT in pituitary adenomas.

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Section: Comparisons Of Cytoplasmic Tert Expression With Clinicopathomentioning

confidence: 99%

“…TErT expression is suppressed in normal adult somatic tissues, but it can be expressed in embryogenic tissues. reactivation of TErT has been detected in approximately 90% of human cancers (3,(17)(18)(19)(20). Thus, TErT activity in pituitary adenomas has been the subject of a few studies that showed contradictory results (3,16,21).…”

Section: Introductionmentioning

confidence: 99%

Tert expression in pituitary adenomas

Can

Çelık²,

Bulbul³

et al. 2017

TJPATH

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“…1) [6,11,12,16,[26][27][28][29][30][31][32]. Those 11 studies involved a total of 3,444 patients with gliomas [6,11,12,16,[26][27][28][29][30][31][32]. Table 1 showed the main characteristics of those 11 included studies in the meta-analysis (Table 1).…”

Section: Characteristics Of Studiesmentioning

confidence: 99%

“…Table 1 showed the main characteristics of those 11 included studies in the meta-analysis (Table 1). Five studies focused on the prognostic role of TERT promoter mutations in patients with gliomas [11,12,28,29,32], five studies focused on the prognostic role of TERT promoter mutations in patients with glioblastoma [6,16,26,30,31], and one study focused on the prognostic role of TERT promoter mutations in patients with medulloblastoma [27]. Among those 11 studies, nine studies reported adjusted HRs [6,11,12,16,26,[28][29][30][31].…”

Section: Characteristics Of Studiesmentioning

confidence: 99%

“…The two most common mutations in the TERT promoter are C228T and C250T, which can lead to a two-to fourfold increased transcriptional activity [7,9]. Previous studies also found that the occurrence of TERT promoter mutations in gliomas was frequent [6,10,11]. So far, several studies on the association between TERT promoter mutations and prognosis of gliomas had been performed, but the conclusion still was not uncertain [6,[12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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Association of Telomerase Reverse Transcriptase Promoter Mutations with the Prognosis of Glioma Patients: a Meta-Analysis

Wang

et al. 2015

Mol Neurobiol

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Previous studies have found that telomerase reverse transcriptase (TERT) has vital roles in the development of malignant diseases including glioma. The occurrence of TERT promoter mutations in gliomas is frequent. So far, several studies on the association between TERT promoter mutations and prognosis of gliomas had been published, but the conclusion was still not uncertain. The aim of the present meta-analysis was to assess the association between TERT promoter mutations and survival of glioma patients by pooling data from published studies. PubMed, Embase, and Web of Science were searched for articles on the association between TERT promoter mutations and survival of glioma patients until June 30, 2015. Hazard ratios (HR) and the 95% confidence intervals (CIs) were utilized to analyze the prognosis of glioma patients with TERT promoter mutations. Heterogeneity of included studies was assessed using Cochrane's Q test and I (2) method. Eleven studies with a total of 3,444 glioma patients were finally included into the meta-analysis. Nine studies reported the HRs adjusting for other confounding factors. Meta-analysis of total 11 studies suggested that TERT promoter mutations were significantly associated with worse prognosis of patients with gliomas (HR = 2.07, 95% CI = 1.58-2.71, P < 0.00001). Meta-analysis of nine studies with adjusted outcomes suggested that TERT promoter mutations were independently associated with worse prognosis of patients with gliomas (HR = 2.28, 95% CI = 1.72-3.01, P < 0.00001). In conclusion, TERT promoter mutation is a promising biomarker for predicting worse prognosis for patients with gliomas. More prospective well-designed cohort studies are needed to further validate its prognostic role in gliomas.

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The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism

Batısta

Cruvinel-Carloni

Vinagre

et al. 2016

Intl Journal of Cancer

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Human hotspot TERT promoter (TERTp) mutations have been reported in a wide range of tumours. Several studies have shown that TERTp mutations are associated with clinicopathological features; in some instances, TERTp mutations were considered as biomarkers of poor prognosis. The rs2853669 SNP, located in the TERT promoter region, was reported to modulate the increased TERT expression levels induced by the recurrent somatic mutations. In this study we aimed to determine the frequency and prognostic value of TERTp mutations and TERT rs2853669 SNP in 504 gliomas from Portuguese and Brazilian patients. TERTp mutations were detected in 47.8% of gliomas (216/452). Glioblastomas (GBM) exhibited the highest frequency of TERTp mutations (66.9%); in this glioma subtype, we found a significant association between TERTp mutations and poor prognosis, regardless of the population. Moreover, in a multivariate analysis, TERTp mutations were the only independent prognostic factor. Our data also showed that the poor prognosis conferred by TERTp mutations was restricted to GBM patients

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TERT Promoter Mutations Lead to High Transcriptional Activity under Hypoxia and Temozolomide Treatment and Predict Poor Prognosis in Gliomas

Cited by 39 publications

References 32 publications

Tert expression in pituitary adenomas

Tert expression in pituitary adenomas

Association of Telomerase Reverse Transcriptase Promoter Mutations with the Prognosis of Glioma Patients: a Meta-Analysis

The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism

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