TERT Promoter Mutations in Keratinizing and Nonkeratinizing Squamous Metaplasia of the Urinary Tract

In the 2016 WHO classification of genitourinary tumors Muellerian tumors of the urinary tract (MTUT) comprise clear cell adenocarcinomas and endometrioid carcinomas. Since these rare tumors remained understudied, we aimed to characterize their molecular background by performing DNA- and RNA-based targeted panel sequencing. All tumors (n = 11) presented single nucleotide alterations (SNVs), with ARID1A mutations being the most prevalent (5/11, 45%). Besides frequent ARID1A mutations, loss of ARID1A protein is not a suitable marker since protein expression is (partly) preserved also in mutated cases. Copy number alterations (CNVs) were found in 64% of cases (7/11), exclusively gene amplifications. Interestingly, a functionally relevant RSPO2 gene fusion/microdeletion was discovered in the endometrioid adenocarcinoma case. Comparing our findings with mutational profiles of other tumor entities, absence of TERT promoter mutations argues for a non-urothelial origin. No similarities were also found between MTUT and kidney cancers while parallels were observed for specific SNVs with endometrial carcinomas. In conclusion, immunohistochemical PAX8-positivity and lack of TERT promoter mutations could serve as key diagnostic features in difficult cases. Thus, understanding the molecular background of these tumors helps to refine treatment options and offers the possibility of targeted therapies in cases where needed.

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Prognostic significance of TERT promoter mutations in follicular cell-derived thyroid carcinomas

Endocrine Abstracts ◽

10.1530/endoabs.35.p1149 ◽

2014 ◽

Author(s):

Miguel Melo ◽

Rocha Adriana Gaspar da ◽

Joao Vinagre ◽

Rui Batista ◽

Joana Peixoto ◽

...

Keyword(s):

Prognostic Significance ◽

Follicular Cell ◽

Thyroid Carcinomas ◽

Tert Promoter ◽

Tert Promoter Mutations ◽

Promoter Mutations

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

Endocrine Abstracts ◽

10.1530/endoabs.37.gp.24.02 ◽

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

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TERT promoter mutations in pancreatic endocrine tumours are frequent in tumours from patients with hereditary syndromes

Endocrine Abstracts ◽

10.1530/endoabs.40.oc4 ◽

2016 ◽

Author(s):

Joao Vinagre ◽

Joana Nabais ◽

Jorge Pinheiro ◽

Rui Batista ◽

Rui Oliveira ◽

...

Keyword(s):

Endocrine Tumours ◽

Hereditary Syndromes ◽

Tert Promoter ◽

Tert Promoter Mutations ◽

Pancreatic Endocrine Tumours ◽

Promoter Mutations

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Faculty Opinions recommendation of TERT promoter mutations in familial and sporadic melanoma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717978928.793472028 ◽

2013 ◽

Author(s):

Philip Mason

Keyword(s):

Tert Promoter ◽

Tert Promoter Mutations ◽

Promoter Mutations

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Faculty Opinions recommendation of TERT Promoter Mutations Are Predictive of Aggressive Clinical Behavior in Patients with Spitzoid Melanocytic Neoplasms.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725547642.793519577 ◽

2016 ◽

Author(s):

Iwei Yeh

Keyword(s):

Clinical Behavior ◽

Tert Promoter ◽

Tert Promoter Mutations ◽

Promoter Mutations ◽

Aggressive Clinical Behavior

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Human TERT promoter mutations as a prognostic biomarker in glioma

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03536-3 ◽

2021 ◽

Vol 147 (4) ◽

pp. 1007-1017

Author(s):

Branka Powter ◽

Sarah A. Jeffreys ◽

Heena Sareen ◽

Adam Cooper ◽

Daniel Brungs ◽

...

Keyword(s):

Clinical Utility ◽

Nucleotide Polymorphism ◽

Liquid Biopsies ◽

Single Nucleotide ◽

Tert Promoter ◽

Tert Promoter Mutations ◽

Potential Clinical Utility ◽

Promoter Mutations ◽

The Relationship ◽

Potential Use

AbstractThe TERT promoter (pTERT) mutations, C228T and C250T, play a significant role in malignant transformation by telomerase activation, oncogenesis and immortalisation of cells. C228T and C250T are emerging as important biomarkers in many cancers including glioblastoma multiforme (GBM), where the prevalence of these mutations is as high as 80%. Additionally, the rs2853669 single nucleotide polymorphism (SNP) may cooperate with these pTERT mutations in modulating progression and overall survival in GBM. Using liquid biopsies, pTERT mutations, C228T and C250T, and other clinically relevant biomarkers can be easily detected with high precision and sensitivity, facilitating longitudinal analysis throughout therapy and aid in cancer patient management.In this review, we explore the potential for pTERT mutation analysis, via liquid biopsy, for its potential use in personalised cancer therapy. We evaluate the relationship between pTERT mutations and other biomarkers as well as their potential clinical utility in early detection, prognostication, monitoring of cancer progress, with the main focus being on brain cancer.

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

Cancers ◽

10.3390/cancers13040648 ◽

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.

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