scholarly journals TERT Promoter Mutation is a Diagnostic and Differential Diagnostic Marker for Tumors with Urothelial Origin

2020 ◽  
Vol 4 (2) ◽  
Author(s):  
Shaobo Zhang
Keyword(s):  
Differential Diagnosis ◽  
Diagnostic Marker ◽  
Clinical Implications ◽  
Telomerase Reverse Transcriptase ◽  
Tert Promoter Mutation ◽  
Promoter Mutation ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Telomerase reverse transcriptase (TERT) promoter mutations have been found in approximately 60–80% of bladder urothelial cancers and its variants of all grades anywhere in the urinary tract. The TERT promoter mutations occur early in urothelial neoplasia and are biomarkers for neoplasm development, recurrence, diagnosis, differential diagnosis, and potentially a therapeutic target. This review highlighted the role of TERT promoter mutations in urothelial tumorigenesis, and the potential clinical implications.

scholarly journals The role of telomerase reverse transcriptase (TERT) promoter mutations in prognosis in bladder cancer

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 1495-1504
Author(s):  
Song Wan ◽  
Xuan Liu ◽  
Wei Hua ◽  
Ming Xi ◽  
Yulin Zhou ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Reverse Transcriptase ◽  
Telomerase Reverse Transcriptase ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Cell-free tumor DNA and TERT promoter mutations in bladder cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 353-353 ◽  
Author(s):  
Franklin W. Huang ◽  
Mikael L. Rinne ◽  
Kevin T. Lundgren ◽  
Stephanie Anne Mullane ◽  
Irene Moreno ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Metastatic Disease ◽  
Tert Promoter Mutation ◽  
Plasma Samples ◽  
Promoter Mutation ◽  
Library Construction ◽  
Non Invasive ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

353 Background: Currently, there are no FDA-approved blood biomarkers for the prognosis or prediction of outcomes in urothelial carcinoma (UC). The telomerase reverse transcriptase ( TERT) promoter is recurrently mutated at high frequency in UC (50%). These mutations have been correlated with tumor recurrence and survival. Tumor cell-free DNA (cfDNA) with somatic genomic alterations can be found in the plasma of cancer patients and has the potential for use as a non-invasive cancer biomarker. Detection of TERT promoter mutations in cfDNA might be used as a prognostic tool to monitor disease outcome in UC patients. We set out to detect tumor cfDNA and TERT promoter mutations in cfDNA from patients with UC at different stages. Methods: UC patients receiving chemotherapy in the neoadjuvant, first or second-line metastatic setting had blood collected either before or during therapy. cfDNA was isolated from ~1ml plasma samples using the QIAmp (Qiagen) kit. Samples underwent ultra-low pass whole genome sequencing (ULP-WGS) to determine whether tumor cfDNA could be detected in these samples. TERT promoter mutations were detected using a sensitive qPCR assay. Results: 40 plasma samples from a total of 32 patients with urothelial carcinoma were analyzed. Sufficient amounts of plasma cfDNA were obtained for library construction and ULP-WGS in 11 patients. 6 of these 11 patients were determined to be positive for detectable tumor cfDNA and of these, all were metastatic and 50% (3/6) were positive for a TERT promoter mutation. In total, 8 out of 40 samples (20%) were positive for a TERT promoter mutation, including samples from two patients where total cfDNA yield was insufficient for library construction. A total of ~20% of patients with metastatic disease were positive for TERT promoter mutations in cfDNA. The low percentage of samples having sufficient cfDNA most likely reflects the low volume of plasma used. Conclusions: TERT promoter mutations were identified in cfDNA of UC patients. ULP-WGS showed tumor cfDNA in patients with a high tumor burden and metastatic disease. TERTpromoter mutations in cfDNA could potentially be used as a non-invasive method for detection of disease. These results have implications for the use of cfDNA in the evaluation of advanced UC.

scholarly journals Prospective Analysis of TERT Promoter Mutations in Papillary Thyroid Carcinoma at a Single Institution

2021 ◽  
Vol 10 (10) ◽  
pp. 2179
Author(s):  
Yun-Suk Choi ◽  
Seong-Woon Choi ◽  
Jin-Wook Yi
Keyword(s):  
Thyroid Cancer ◽  
Surgical Margin ◽  
Tert Promoter Mutation ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Promoter Mutation ◽  
Large Tumor ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Background: Papillary thyroid cancer (PTC) has the highest cancer incidence in Korea. It is known that some thyroid cancers have aggressive clinical behavior and a poor prognosis. Genomic studies have described some somatic mutations that are related to the aggressive features of thyroid cancer, such as the BRAFV600E mutation. Recently, TERT promoter mutations were identified and reported as poor prognostic factors in PTC. Our aim was to identify the frequency and clinical impact of TERT promoter mutation in PTC. Methods: Analysis of both BRAFV600E and TERT promoter mutations in thyroidectomy specimens began in February 2019. As of December 2020, 622 patients had been tested. Data were prospectively collected and retrospectively reviewed to ascertain clinical and pathologic variables. Results: TERT promoter mutations were identified in 13 patients (2.09%); 12 had the C228T mutation, and one had the C216T mutation. In total, ten patients had the BRAFV600E mutation. TERT promoter mutation was significantly associated with advanced age (46.795 ± 12.616 versus 65.692 ± 13.628 years, p < 0.001), large tumor size (1.006 ± 0.829 versus 2.285 ± 1.938 cm, p = 0.035), extrathyroidal extension, surgical margin involvement, angioinvasion, BRAFV600E mutation and advanced TNM stage, a higher MACIS score and a high proportion of radioactive iodine therapy application. Logistic regression showed that lymphatic and angioinvasion and BRAFV600E mutation were predictive of TERT promoter mutation. Conclusions: Our study is the first to report the prospective results of TERT promoter mutations at a single tertiary hospital in Incheon, Korea. PTC with TERT promoter mutation was associated with more aggressive behavior than PTC with wild-type TERT gene status.

scholarly journals TB-04 TERT PROMOTER MUTATION AS A SUSCEPTIBLE MOLECULAR MARKER OF BCNU LOCAL THERAPY

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii10-ii11
Author(s):  
Shigeta Miyake ◽  
Kensuke Tateishi ◽  
Joe Sasame ◽  
Yohei Miyake ◽  
Shinichirou Matsuyama ◽  
...  
Keyword(s):  
Molecular Marker ◽  
Methylation Status ◽  
Malignant Gliomas ◽  
Local Therapy ◽  
Tert Promoter Mutation ◽  
Mgmt Methylation ◽  
Promoter Mutation ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Abstract INTRODUCTION Alkylating agents, including Temozolomide (TMZ) and CCNU (ACNU) have been widely accepted as a standard treatment in malignant gliomas. Several studies also demonstrated that BCNU wafer placement extended survival in glioblastoma patients. However, little study demonstrated gene-specific efficacy of BCNU local therapy in malignant gliomas. Herein, we investigated BCNU sensitivity for patient-derived primary cultured glioma cells. MATERIALS AND METHODS From January 2017 to July 2019, 58 gliomas (grade III, IV) were tested genomic analysis and ATP-based cell viability after BCNU treatment. IDH1/2 mutation and TERT promoter mutation status was determined by Sanger sequencing. MGMT methylation status were evaluated by methylation specific PCR. RESULTS Of 58 cases,10 cases (17.2%) and 32 (55.2%) cases harbored IDH1/2 mutation and TERT mutation (C228T, C250T), respectively. Among them, co-mutation was identified in 5/58 cases (8.6%). MGMT was methylated in 17/58 cases (29.3%). Interestingly, the presence of TERT promoter mutation was positively correlated with BCNU sensitivity, particularly in IDH1/2 wild-type tumors (p&lt;0.05). In contrast, there was no significant relationship between TMZ sensitivity and IDH mutation/MGMT methylation status. CONCLUSION Although sample size is small, our results imply TERT promoter mutations might be a predictive molecular marker for BCNU sensitivity in malignant gliomas. Since TERT mutations are located at two hot spot loci (C228T and C250T), vast majority of TERT promoter mutations can be evaluated during surgery, which may contribute tailored therapeutic strategy in malignant gliomas.

scholarly journals BIOM-59. TERT PROMOTER MUTATION AND MGMT PROMOTER METHYLATION-MEDIATED SENSITIVITY TO TEMOZOLOMIDE IN IDH-WILDTYPE GLIOBLASTOMA: IS THERE A LINK?

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii14-ii14
Author(s):  
Dorothee Gramatzki ◽  
Jörg Felsberg ◽  
Bettina Hentschel ◽  
Marietta Wolter ◽  
Gabriele Schackert ◽  
...  
Keyword(s):  
Promoter Methylation ◽  
Mgmt Promoter Methylation ◽  
Tert Promoter Mutation ◽  
Promoter Mutation ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Mgmt Promoter ◽  
Hotspot Mutations ◽  
Promoter Mutations ◽  
The Impact

Abstract BACKGROUND Benefit from temozolomide (TMZ) chemotherapy in the treatment of isocitrate dehydrogenase (IDH)-wildtype glioblastoma is essentially limited to patients with O6-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumors. Recent studies suggest that the impact of the MGMT status on chemosensitivity may be modulated by telomerase reverse transcriptase (TERT) promoter hotspot mutations. METHODS MGMT promoter methylation and TERT promoter mutation status were assessed in an exploratory prospective cohort of IDH-wildtype glioblastoma patients of the German Glioma Network (GGN) (n=298) and validated in a retrospective cohort from Düsseldorf, Germany, and Zurich, Switzerland (n=302). RESULTS In the prospective GGN discovery cohort of patients with MGMT promoter-unmethylated tumors, TERT promoter mutation showed inferior outcome (p=0.044). In contrast, TERT promoter mutations were not associated with improved outcome in patients with MGMT promoter-methylated tumors. Different TERT promoter hotspot mutations were not associated with distinct outcomes. The association of TERT promoter mutation in MGMT promoter-unmethylated tumors was not confirmed in the retrospective validation cohort. CONCLUSIONS Analysis of two independent cohorts of glioblastoma patients, including the prospective GGN cohort, did not confirm previous data suggesting that TERT promoter mutations confer an enhanced benefit from TMZ in patients with MGMT promoter-methylated glioblastoma. Thus, diagnostic testing for TERT promoter mutations may not be required for prediction of TMZ sensitivity in IDH-wildtype glioblastoma patients.

scholarly journals Molecular Genetics of Conjunctival Melanoma and Prognostic Value of TERT Promoter Mutation Analysis

2021 ◽  
Vol 22 (11) ◽  
pp. 5784
Author(s):  
Natasha M. van Poppelen ◽  
Jolique A. van Ipenburg ◽  
Quincy van den Bosch ◽  
Jolanda Vaarwater ◽  
Tom Brands ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Molecular Data ◽  
P Value ◽  
Tert Promoter Mutation ◽  
Conjunctival Melanoma ◽  
Promoter Mutation ◽  
Molecular Features ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

The aim of this study was exploration of the genetic background of conjunctival melanoma (CM) and correlation with recurrent and metastatic disease. Twenty-eight CM from the Rotterdam Ocular Melanoma Study group were collected and DNA was isolated from the formalin-fixed paraffin embedded tissue. Targeted next-generation sequencing was performed using a panel covering GNAQ, GNA11, EIF1AX, BAP1, BRAF, NRAS, c-KIT, PTEN, SF3B1, and TERT genes. Recurrences and metastasis were present in eight (29%) and nine (32%) CM cases, respectively. TERT promoter mutations were most common (54%), but BRAF (46%), NRAS (21%), BAP1 (18%), PTEN (14%), c-KIT (7%), and SF3B1 (4%) mutations were also observed. No mutations in GNAQ, GNA11, and EIF1AX were found. None of the mutations was significantly associated with recurrent disease. Presence of a TERT promoter mutation was associated with metastatic disease (p-value = 0.008). Based on our molecular findings, CM comprises a separate entity within melanoma, although there are overlapping molecular features with uveal melanoma, such as the presence of BAP1 and SF3B1 mutations. This warrants careful interpretation of molecular data, in the light of clinical findings. About three quarter of CM contain drug-targetable mutations, and TERT promoter mutations are correlated to metastatic disease in CM.

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