scholarly journals Rare TERT Promoter Mutations Present in Benign and Malignant Cutaneous Vascular Tumors

Dermato ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 18-25
Author(s):  
Philipp Jansen ◽  
Georg Christian Lodde ◽  
Anne Zaremba ◽  
Carl Maximilian Thielmann ◽  
Johanna Matull ◽  
...  
Keyword(s):  
Vascular Malformations ◽  
Hot Spot ◽  
Vascular Tumors ◽  
General Description ◽  
Targeted Next Generation Sequencing ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Low Prevalence ◽  
Next Generation Sequencing Ngs ◽  
Promoter Mutations

Mutations in the promoter of the telomerase reverse transcriptase (TERT) gene have been described as the most common hot-spot mutations in different solid tumors. High frequencies of TERT promoter mutations have been reported to occur in tumors arising in tissues with low rates of self-renewal. For cutaneous vascular tumors, the prevalence of TERT promoter mutations has not yet been investigated in larger mixed cohorts. With targeted next-generation sequencing (NGS), we screened for different known recurrent TERT promoter mutations in various cutaneous vascular proliferations. In our cohort of 104 representative cutaneous vascular proliferations, we identified 7 TERT promoter mutations. We could show that 4 of 64 (6.3%) hemangiomas and vascular malformations harbored TERT promoter mutations (1 Chr.5:1295228 C > T mutations, 1 Chr.5:1295228_9 CC > TT mutation, and 2 Chr.5:1295250 C > T mutations), 1 of 19 (5.3%) angiosarcomas harbored a Chr.5:1295250 C > T TERT promoter mutation, and 2 of 21 (9.5%) Kaposi’s sarcomas harbored TERT promoter mutations (2 Chr.5:1295250 C > T mutations). To our knowledge, this is the first general description of the distribution of TERT promoter mutations in a mixed cohort of cutaneous vascular tumors, revealing that TERT promoter mutations seem to occur with low prevalence in both benign and malignant cutaneous vascular proliferations.

scholarly journals Hot Spot TERT Promoter Mutations Are Rare in Sporadic Pancreatic Neuroendocrine Neoplasms and Associated with Telomere Length and Epigenetic Expression Patterns

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1625
Author(s):  
Alexandra Posch ◽  
Sarah Hofer-Zeni ◽  
Eckhard Klieser ◽  
Florian Primavesi ◽  
Elisabeth Naderlinger ◽  
...  
Keyword(s):  
Telomere Length ◽  
Hot Spot ◽  
Expression Profiles ◽  
Ffpe Tissue ◽  
Telomere Maintenance ◽  
Neuroendocrine Neoplasms ◽  
Pancreatic Neuroendocrine Neoplasms ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Cancer cells activate a telomere maintenance mechanism like telomerase in order to proliferate indefinitely. Telomerase can be reactivated by gain-of-function Telomerase Reverse Transcriptase (TERT) promoter mutations (TPMs) that occur in several cancer subtypes with high incidence and association with diagnosis, prognosis and epigenetics. However, such information about TPMs in sporadic pancreatic neuroendocrine neoplasms (pNENs) including tumor (pNET) and carcinoma (pNEC) is less well defined. We have studied two hot spot TPMs and telomere length (TL) in pNEN and compared the results with clinicopathological information and proliferation-associated miRNA/HDAC expression profiles. DNA was isolated from formalin-fixed paraffin-embedded (FFPE) tissue of 58 sporadic pNEN patients. T allele frequency of C250T and C228T TPM was analyzed by pyrosequencing, relative TL as telomeric content by qPCR. In total, five pNEN cases (9%) including four pNETs and one pNEC were identified with TPMs, four cases with exclusive C250T as predominant TPM and one case with both C250T and C228T. T allele frequencies of DNA isolated from adjacent high tumor cell content FFPE tissue varied considerably, which may indicate TPM tumor heterogeneity. Overall and disease-free survival was not associated with TPM versus wild-type pNEN cases. Binary category analyses indicated a marginally significant relationship between TPM status and longer telomeres (p = 0.086), and changes in expression of miR449a (p = 0.157), HDAC4 (p = 0.146) and HDAC9 (p = 0.149). Future studies with larger patient cohorts are needed to assess the true clinical value of these rare mutations in pNEN.

scholarly journals Low Prevalence of Somatic TERT Promoter Mutations in Classic Papillary Thyroid Carcinoma

2016 ◽  
Vol 31 (1) ◽  
pp. 100 ◽  
Author(s):  
Min Ji Jeon ◽  
Won Gu Kim ◽  
Soyoung Sim ◽  
Seonhee Lim ◽  
Hyemi Kwon ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Papillary Thyroid ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Low Prevalence ◽  
Promoter Mutations

scholarly journals TERT Promoter Mutation Analysis of Whole-Organ Mapping Bladder Cancers

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 230
Author(s):  
Veronika Weyerer ◽  
Markus Eckstein ◽  
Pamela L. Strissel ◽  
Adrian Wullweber ◽  
Fabienne Lange ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Telomere Length ◽  
Hot Spot ◽  
Tumor Development ◽  
Non Invasive ◽  
Tert Promoter ◽  
Mutational Status ◽  
Tert Promoter Mutations ◽  
Promoter Mutations ◽  
Normal Urothelium

Background: Multifocal occurrence is a main characteristic of urothelial bladder cancer (UBC). Whether urothelial transformation is caused by monoclonal events within the urothelium, or by polyclonal unrelated events resulting in several tumor clones is still under debate. TERT promoter mutations are the most common somatic alteration identified in UBC. In this study, we analyzed different histological tissues from whole-organ mapping bladder cancer specimens to reveal TERT mutational status, as well as to discern how tumors develop. Methods: Up to 23 tissues from nine whole-organ mapping bladder tumor specimens, were tested for TERT promoter mutations including tumor associated normal urothelium, non-invasive urothelial lesions (hyperplasia, dysplasia, metaplasia), carcinoma in situ (CIS) and different areas of muscle invasive bladder cancers (MIBC). The mutational DNA hotspot region within the TERT promoter was analyzed by SNaPshot analysis including three hot spot regions (−57, −124 or −146). Telomere length was measured by the Relative Human Telomere Length Quantification qPCR Assay Kit. Results: TERT promoter mutations were identified in tumor associated normal urothelium as well as non-invasive urothelial lesions, CIS and MIBC. Analysis of separate regions of the MIBC showed 100% concordance of TERT promoter mutations within a respective whole-organ bladder specimen. Polyclonal events were observed in five out of nine whole-organ mapping bladder cancers housing tumor associated normal urothelium, non-invasive urothelial lesions and CIS where different TERT promoter mutations were found compared to MIBC. The remaining four whole-organ mapping bladders were monoclonal for TERT mutations. No significant differences of telomere length were observed. Conclusions: Examining multiple whole-organ mapping bladders we conclude that TERT promoter mutations may be an early step in bladder cancer carcinogenesis as supported by TERT mutations detected in tumor associated normal urothelium as well as non-invasive urothelial lesions. Since mutated TERT promoter regions within non-invasive urothelial lesions are not sufficient alone for the establishment of cancerous growth, this points to the contribution of other gene mutations as a requirement for tumor development.

TERT Immunohistochemistry Expression as a Surrogate of TERT Promoter Mutations in Infiltrating Gliomas

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S142-S142
Author(s):  
A M Moosvi ◽  
A Dono ◽  
A Bellman ◽  
L Ballester ◽  
P Goli ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Surrogate Marker ◽  
Study Cohort ◽  
Targeted Next Generation Sequencing ◽  
Tert Promoter Mutations ◽  
Next Generation Sequencing Ngs ◽  
Promoter Mutations ◽  
Generation Sequencing

Abstract Introduction/Objective Genomic alterations are critical for the diagnosis of infiltrating gliomas. Mutations in the telomerase reverse transcriptase promoter (TERTp) are sufficient for a diagnosis of glioblastoma in some cases, independent of histologic features. Although DNA sequencing is the preferred method for evaluating TERTp mutations, there are limitations with regards to turn-around-time, accessibility, and cost. In this study, we evaluated the efficacy of using TERT immunohistochemistry (IHC) as a surrogate marker for the identification of TERTp mutations in infiltrating gliomas. Methods/Case Report The study cohort consisted of 31 infiltrating gliomas diagnosed following the 2016 WHO classification of CNS tumors by a board-certified neuropathologist. Each case was evaluated by immunohistochemistry (anti-TERT monoclonal antibody) and with a targeted next-generation sequencing (NGS) panel. A systemic literature search was conducted to examine reports of TERT antibody as a surrogate marker of TERTp mutations. TERTp mutation detected by sequencing was considered the gold standard. Results (if a Case Study enter NA) TERT immunohistochemistry demonstrated a sensitivity of 61.1% and specificity of 69.2%. Cases were divided into IDH-WT and IDH-mutant infiltrating gliomas. Among the IDH-WT group, 84% contained the TERTp mutation with a sensitivity of 62.5% and specificity of 33.3% for the TERTp IHC. IDH-mutant gliomas showed a 16.2% TERTp mutation rate, and immunohistochemistry had a sensitivity of 50% and 80% specificity. The probability of TERT immunohistochemistry in diagnosing TERTp mutations exhibited a poor likelihood ratio for both the positive and negative test. Literature review included 5 studies with an overall sensitivity and specificity remaining consistently low (<80%), with 2 of these studies evaluating CNS related tumors giving rise to similar diagnostic performance. Conclusion TERT IHC has suboptimal sensitivity and specificity for identifying TERTp mutations in IDH-WT and IDH- mutant infiltrating gliomas.

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

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

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 Human TERT promoter mutations as a prognostic biomarker in glioma

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.

Sign in / Sign up

Export Citation Format

Share Document