scholarly journals TERT promoter mutations in thyroid cancer

2016 ◽  
Vol 23 (3) ◽  
pp. R143-R155 ◽  
Author(s):  
Rengyun Liu ◽  
Mingzhao Xing
Keyword(s):  
Thyroid Cancer ◽  
Genetic Markers ◽  
Tumor Recurrence ◽  
Anaplastic Thyroid Cancer ◽  
Thyroid Tumor ◽  
Cancer Field ◽  
Tert Promoter Mutations ◽  
Poorly Differentiated ◽  
Promoter Mutations

The 2013 discovery of Telomerase reverse transcriptase (TERT) promoter mutations chr5, 1,295,228 C>T (C228T) and 1,295,250 C>T (C250T) in thyroid cancer represents an important event in the thyroid cancer field and much progress has occurred since then. This article provides a comprehensive review of this exciting new thyroid cancer field. The oncogenic role of TERT promoter mutations involves their creation of consensus binding sites for E-twenty-six transcriptional factors. TERT C228T is far more common than TERT C250T and their collective prevalence is, on average, 0, 11.3, 17.1, 43.2 and 40.1% in benign thyroid tumors, papillary thyroid cancer (PTC), follicular thyroid cancer, poorly differentiated thyroid cancer and anaplastic thyroid cancer, respectively, displaying an association with aggressive types of thyroid cancer. TERT promoter mutations are associated with aggressive thyroid tumor characteristics, tumor recurrence and patient mortality as well as BRAF V600E mutation. Coexisting BRAF V600E and TERT promoter mutations have a robust synergistic impact on the aggressiveness of PTC, including a sharply increased tumor recurrence and patient mortality, while either mutation alone has a modest impact. Thus, TERT with promoter mutations represents a prominent new oncogene in thyroid cancer and the mutations are promising new diagnostic and prognostic genetic markers for thyroid cancer, which, in combination with BRAF V600E mutation or other genetic markers (e.g. RAS mutations), are proving to be clinically useful for the management of thyroid cancer. Future studies will specifically define such clinical utilities, elucidate the biological mechanisms and explore the potential as therapeutic targets of TERT promoter mutations in thyroid cancer.

scholarly journals Bioinformatic analysis and identification of potential hallmarks in poorly differentiated thyroid cancer

2021 ◽  
Author(s):  
Xin Chen ◽  
Runsheng Ma ◽  
Hongqiang Li ◽  
Yifeng Tang ◽  
Detao Yin
Keyword(s):  
Thyroid Cancer ◽  
Malignant Transformation ◽  
Differentiated Thyroid Cancer ◽  
Anaplastic Thyroid Cancer ◽  
Bioinformatic Analysis ◽  
Thyroid Tumor ◽  
High Expression ◽  
Hub Genes ◽  
Expression Levels ◽  
Poorly Differentiated

Abstract Purpose: The accumulation of malignant tumor gene mutations makes differentiated thyroid cancer (DTC) gradually dedifferentiated to poorly differentiated thyroid cancer (PDTC) or anaplastic thyroid cancer (ATC). This study analyzed the gene expression profile in the process of dedifferentiation of thyroid cancer, aiming to explore the molecular mechanism of PDTC and ATC.Methods: Eight series from GEO database are collected for differentially expressed genes (DEGs) of DTC, PDTC and ATC. Then, GO analysis, KEGG pathway analysis, and functional path enrichment analyses are performed by MATESCAPE. Hub-genes are identified by using the method of MNC in protein interaction networks. Moreover, the expression of hub-genes and hub-gene related survival in thyroid cancers are analyzed by GEPIA2. Finally, the functional path enrichment pathways of PDTC are performed by GSEA Java.Results: There are obvious differences among DEGs of DTC, PDTC, and ATC, and 17 cross gene of DEGs were found. The DEGs in PDTC were mainly concentrated in regulation of cytoskeleton organization, cell division, positive regulation of kinase activity. While the DEGs in ATC were mainly in extracellular matrix organization, extracellular structure organization. Furthermore, 6 hub-genes were obtained in the development of PDTC by using Cytoscape: EGF, CCND1, DEPDC1, ANLN, HGF, BCL2L1. The high expression levels of the genes of EGF, DEPDC1, ANLN, HGF were associated with the poor survival of thyroid cancer. While the high expression levels of CCND1 and BCL2L1 were beneficial to the survival of patients with thyroid tumor. Finally, GSEA revealed that two gene sets are significantly enriched, including KEGG_THYROID_CANCER and KEGG_GLIOMA. And CCND1 and EGF have a core gene position in KEGG_GLIOMA.Conclusions: The molecular function (MF), biological processes (BP) and KEGG pathways have changed during the process of malignant transformation of thyroid cancer. Especially, the activation of EGF-EGFR pathway promotes the malignant transformation of thyroid tumor. Furthermore, six hub-genes, especially CCND1 and EGF, could become potential biomarkers of PDTC. This study can serve as a reference to understand the malignant transformation of thyroid cancer.

In papillary thyroid cancer TERT promoter mutations have a worst impact on outcome than BRAF mutations

2015 ◽  
Author(s):  
Marina Muzza ◽  
Carla Colombo ◽  
Maria Carla Proverbio ◽  
Stefania Rossi ◽  
Delfina Tosi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Papillary Thyroid ◽  
Braf Mutations ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

scholarly journals TERT Promoter Mutations and the 8th Edition TNM Classification in Predicting the Survival of Thyroid Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 648
Author(s):  
Jun Park ◽  
Sungjoo Lee ◽  
Kyunga Kim ◽  
Hyunju Park ◽  
Chang-Seok Ki ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Prognostic Factor ◽  
Histologic Type ◽  
Stage At Diagnosis ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Specific Mortality ◽  
Cancer Specific Mortality ◽  
Promoter Mutations ◽  
8Th Edition

Our research group has previously shown that the presence of TERT promoter mutations is an independent prognostic factor, by applying the TERT mutation status to the variables of the AJCC 7th edition. This study aimed to determine if TERT mutations could be independent predictors of thyroid cancer-specific mortality based on the AJCC TNM 8th edition, with long-term follow-up. This was a retrospective study of 393 patients with pathologically confirmed differentiated thyroid carcinoma (DTC) after thyroidectomy at a tertiary Korean hospital from 1994 to 2004. The thyroid cancer-specific mortality rate was 6.9% (5.2% for papillary and 15.2% for follicular cancers). TERT promoter mutations were identified in 10.9% (43/393) of DTC cases (9.8% of papillary and 16.7% of follicular cancer) and were associated with older age (p < 0.001), the presence of extrathyroidal invasion (p < 0.001), distant metastasis (p = 0.001), and advanced stage at diagnosis (p < 0.001). The 10-year survival rate in mutant TERT was 67.4% for DTC patients (vs. 98% for wild-type; adjusted hazard ratio (HR) of 9.93, (95% CI: 3.67–26.90)) and 75% for patients with papillary cancer (vs. 99%; 18.55 (4.83–71.18)). In addition, TERT promoter mutations were related to poor prognosis regardless of histologic type (p < 0.001 for both papillary and follicular cancer) or initial stage (p < 0.001, p = 0.004, and p = 0.086 for stages I, II, and III and IV, respectively). TERT promoter mutations comprise an independent poor prognostic factor after adjusting for the clinicopathological risk factors of the AJCC TNM 8th edition, histologic type, and each stage at diagnosis, which could increase prognostic predictability for patients with DTC.

scholarly journals Poorly Differentiated and Anaplastic Thyroid Cancer: Insights into Genomics, Microenvironment and New Drugs

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3200
Author(s):  
Alessandro Prete ◽  
Antonio Matrone ◽  
Carla Gambale ◽  
Liborio Torregrossa ◽  
Elisa Minaldi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Thyroid Cancer ◽  
Median Overall Survival ◽  
Clinical Problem ◽  
Anaplastic Thyroid Cancer ◽  
New Drugs ◽  
Poor Survival ◽  
Tumor Microenvironments ◽  
Genetic Features ◽  
Poorly Differentiated

PDTC and ATC present median overall survival of 6 years and 6 months, respectively. In spite of their rarity, patients with PDTC and ATC represent a significant clinical problem, because of their poor survival and the substantial inefficacy of classical therapies. We reviewed the newest findings about genetic features of PDTC and ATC, from mutations occurring in DNA to alterations in RNA. Therefore, we describe their tumor microenvironments (both immune and not-immune) and the interactions between tumor and neighboring cells. Finally, we recapitulate how this upcoming evidence are changing the treatment of PDTC and ATC.

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

scholarly journals TERT promoter mutations in thyroid cancer: growing evidence for a predictor of poor outcome

Gland Surgery ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 301-303 ◽  
Author(s):  
Jianliang Man ◽  
Norman Nicolson ◽  
Courtney Gibson ◽  
Tobias Carling
Keyword(s):  
Thyroid Cancer ◽  
Poor Outcome ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

scholarly journals Impact of BRAF V600E and TERT Promoter Mutations on Response to Therapy in Papillary Thyroid Cancer

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2328-2338 ◽  
Author(s):  
Tomasz Trybek ◽  
Agnieszka Walczyk ◽  
Danuta Gąsior-Perczak ◽  
Iwona Pałyga ◽  
Estera Mikina ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Response To Therapy ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Tumor Node Metastasis ◽  
Node Metastasis ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Abstract In this study, we examined the relationship between coexisting BRAF V600E and TERT promoter mutations in papillary thyroid cancer (PTC) and response to therapy. PTC cases (n = 568) with known BRAF and TERT status, diagnosed from 2000 to 2012 and actively monitored at one institution, were reviewed retrospectively. Associations between BRAF V600E and TERT promoter mutations and clinicopathological features, Tumor-Node-Metastasis stage, initial risk, response to therapy, follow-up, and final disease outcome were assessed according to American Thyroid Association 2015 criteria and the American Joint Committee on Cancer/Tumor-Node-Metastasis (8th edition) staging system. Median follow-up was 120 months. TERT promoter mutations (any type) were detected in 13.5% (77/568) of PTC cases with known BRAF status. The C228T and C250T TERT hotspot mutations were found in 54 (9.5%) and 23 (4%) patients, respectively, and 22 other TERT promoter alterations were identified. Coexisting BRAF V600E and TERT hotspot promoter mutations were detected in 9.5% (54/568) of patients, and significantly associated with older patient age (P = 0.001), gross extrathyroidal extension (P = 0.003), tumor stage pT3-4 (P = 0.005), stage II to IV (P = 0.019), intermediate or high initial risk (P = 0.003), worse than excellent response to primary therapy (P = 0.045), recurrence (P = 0.015), and final outcome of no remission (P = 0.014). We conclude that coexisting BRAF V600E and TERT mutations in patients with PTC are associated with poor initial prognostic factors and clinical course and may be useful for predicting a worse response to therapy, recurrence, and poorer outcome than in patients without the above mutations.

Poorly Differentiated and Anaplastic Thyroid Cancer

2006 ◽  
Vol 13 (2) ◽  
pp. 119-128 ◽  
Author(s):  
Kepal N. Patel ◽  
Ashok R. Shaha
Keyword(s):  
Thyroid Cancer ◽  
Anaplastic Thyroid Cancer ◽  
Poorly Differentiated
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