scholarly journals Molecular Characterization of Muellerian Tumors of the Urinary Tract

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 880
Author(s):  
Nadina Ortiz-Brüchle ◽  
Sophie Wucherpfennig ◽  
Michael Rose ◽  
Stefan Garczyk ◽  
Simone Bertz ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Treatment Options ◽  
Endometrioid Adenocarcinoma ◽  
Diagnostic Features ◽  
Dna And Rna ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Endometrial Carcinomas ◽  
Promoter Mutations ◽  
Suitable Marker

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.

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

2022 ◽  
Vol 35 ◽  
pp. 74-78
Author(s):  
Alexander S. Taylor ◽  
Brandon Newell ◽  
Arul M. Chinnaiyan ◽  
Khaled S. Hafez ◽  
Alon Z. Weizer ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Squamous Metaplasia ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

scholarly journals 214 The effect of Anti-PD-1 therapy on median overall survival and progression free survival in glioblastoma multiforme patients with certain tumor markers

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A233-A233
Author(s):  
Awais Paracha ◽  
Jian Campian
Keyword(s):  
Tumor Markers ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Free Survival ◽  
Tumor Mutation Burden ◽  
Tert Promoter ◽  
Mutation Burden ◽  
Idh Mutations ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

BackgroundAlmost 1 in 6 malignant brain cancers are Glioblastoma Multiforme, relative to most other brain cancers it is the most aggressive and prevalent by the numbers.1 Even with the best treatment options median Overall Survival(OS) remains morbid at 14.6 months and Progression Free Survival(PFS) remains 6.9 months.2 Telomerase Reverse Transcriptase promoter mutations,3 Isocitrate Dehydrogenase(IDH) mutations,4 and Tumor Mutation Burden(TMB)5 are three prominent tumor markers that are known to be associated with better PFS and OS; markers like these in the presence of new therapies maybe prove crucial to the development of novel therapies. Immunotherapy has been dubbed a ‘game changer’ in certain hematological and solid malignancies. Specifically, PD1 is a glycoprotein that is a strong negative regulator of the immune system, by blocking this glycoprotein Anti-PD-1 agents harness a strong response by the immune system to fight a malignancy6. In conjunction with these new found tumor markers, Anti-PD-1 agents maybe the solution that could dramatically improve OS and PFS in these patients.MethodsThe goal of this study was to retrospectively analyze patients‘ charts who had received Anti-PD-1 therapy and had TERT promoter mutations, IDH mutations, different TMBs, and other markers and to compare their OS and PFS outcomes with conventional therapies and their response to immunotherapy.ResultsUpon analyzing the data the presence of a TERT promoter 124C>T mutation, IDH wildtype, and lower TMB gave much better OS and PFS after treatment in patients on Anti-PD1 therapy.ConclusionsAlthough this was a small study, these results certainly can be used to examine larger subsets of patients with these markers receiving immunotherapy because they had definitively better outcomes as compared to status quo treatment options.Ethics ApprovalThe study was approved by Washington University Ethics Board, approval number 201111001.ReferencesDavis, M.E., Glioblastoma: overview of disease and treatment. Clinical journal of oncology nursing, 2016;20(5 Suppl): p. S2–S8.Stupp R, et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal of Medicine 2005;352(10): p. 987–996.Mosrati MA, et al., TERT promoter mutations and polymorphisms as prognostic factors in primary glioblastoma. Oncotarget 2015;6(18): p. 16663–16673.Chen J-R., et al., Isocitrate Dehydrogenase (IDH)1/2 Mutations as Prognostic Markers in Patients With Glioblastomas. Medicine, 2016;95(9): p. e2583–e2583.Wu Y, et al. The predictive value of tumor mutation burden on efficacy of immune checkpoint inhibitors in cancers: a systematic review and meta-analysis. Frontiers in Oncology 2019;9:p. 1161–1161.Almåsbak H, Aarvak T, and Vemuri MC, CAR T. Cell Therapy: a game changer in cancer treatment. Journal of Immunology Research 2016;2016:p. 5474602–5474602.

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.

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 Preoperative detection of the TERT promoter mutations in papillary thyroid carcinomas

2021 ◽  
Author(s):  
Tomoe Nakao ◽  
Michiko Matsuse ◽  
Vladimir Saenko ◽  
Tatiana Rogounovitch ◽  
Aya Tanaka ◽  
...  
Keyword(s):  
Papillary Thyroid ◽  
Thyroid Carcinomas ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations
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