The study of Brazilian NSCLC samples by RT-qPCR showed that LUSC and LUAD express high amounts of TERT and that although the mean TRF size of tumor samples was shorter compared to normal cells, telomeres in NSCLC are probably maintained by telomerase.
The tumors were subtyped by gene expression profiling and analyzed for hotspot mutations in FGFR3, PIK3CA and TERT, the most frequent early driver mutations in this tumor type.
Therefore, the development of telomere-based therapies such as nucleoside analogs, non-nucleoside small molecules, antisense technology, ribozymes, and dominant negative human telomerase reverse transcriptase are being prioritized for eradicating a majority of tumors.
Telomerase activity and (human) Telomerase Reverse Transcriptase (hTERT) expression are considered hallmarks in oncogenesis of neoplasms and are upregulated by alterations of the hTERT promoter.
The effect of allergy on survival was significant (p = 0.025, HR 0.525, 95% CI 0.299-0.924), independent of the effect of chromosome 1p (p < 0.001, HR 93.4, 95% CI 16-546) and 19q (p = 0.801, HR 1.2, 95% CI 0.23-6.9) codeletion or TP53 mutation (p = 0.015, HR 2.7, 95% CI 1.2-5.9), unrelated to TERT expression (p = 0.365, HR 1.1, 95% CI 0.89-1.4) or ATRX mutation (p = 0.904, HR 1.04, 95% CI 0.51-2.14), independent of tumor grade (grade 2 versus grade 3, p = 0.004, HR 2.2, 95% CI 1.3-3.8), not independent of histology (oligodendroglioma and oligoastrocytoma, NOS versus astrocytoma, p = 0.08, HR 0.62, 95% CI 0.36-1.1).
Multivariate analysis incorporating tumor status based on the presence of <i>IDH</i> mutations, <i>TERT</i> promoter mutations, and 1p/19q codeletion showed that in lower-grade gliomas, high NLR predicted poorer survival for the triple-negative, IDH mutation only, TERT mutation only, and IDH and TERT mutation groups.
These genetic rearrangements lead to TERT mRNA expression levels hundreds of times higher than normal, causing increased telomerase activation in these tumors.
Human telomerase reverse transcriptase protein expression predicts tumour aggressiveness and survival in patients with clear cell renal cell carcinoma.
Given that telomerase reverse transcriptase promotor mutations are thought to play a role in progression of other tumor types, the function of telomerase reverse transcriptase mutations in BRAF mutated low-grade serous carcinoma deserves investigation.
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 further found a significant interaction between median k<sub>ep</sub> and K<sup>trans</sup> and TERT status, respectively, suggesting greater risk of death with increasing blood-brain barrier dysfunction in TERT-mutated but not in TERT-wildtype tumors.
Levels of breakpoint t(12;16) and TERTC228T ctDNA correlated with the clinical course and tumor burden in patients with myxoid liposarcomas (n = 4). ctDNA could detect minimal residual disease and tumor recurrence.
Thus, we evaluated the effects of exercise intensity (moderate vs. high-intensity domain) on gene expression of senescence markers Checkpoint kinase 2 and tumor suppressor (<i>Chk2</i> and <i>p53</i>, respectively), shelterin telomere repeat binding 1 and 2 (<i>Trf1</i>/<i>Trf2</i>), DNA repair (<i>Xrcc5</i>), telomerase reverse transcriptase (<i>mTERT</i>) and telomere length in middle aged mice.
Secondary genetic alterations overcome tumor suppressive mechanisms and allow the progression to intermediate lesions characterized by TERT-p mutation or to invasive melanomas displaying disruption of tumor suppressor genes.
CTLA-4 blockade synergized more than Treg depletion with TERT DNA vaccine, suggesting that the effect of CTLA-4 blockade is more likely due to the expansion of effector T cells in the tumor rather than a reduction in the frequency of Tregs.
Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy.
The high frequency of <i>hTERT</i>-promoting mutations and the increased expression of <i>hTERT</i> mRNA in anaplastic thyroid cancer (ATC) make TERT a suitable molecular target for the treatment of this lethal neoplasm.
Telomerase reverse transcriptase (<i>TERT</i>) promoter mutations have been linked to adverse clinical parameters in thyroid cancer, but <i>TERT</i>-expressing tumours are not always mutated.
TERT protein overexpression was noted in 20.1% of our PTC cohort and was significantly associated with poor prognostic markers such as older age, extrathyroidal extension and Stage IV tumors.
Our study uncovers a robust dependency of NRAS-mutant melanoma on TERT, and provides proof-of-principle for a new combination strategy to combat this class of tumors, which could be expanded to other tumor types.
Herein, we review the genomic profiles that have been defined for the different subtypes of pediatric melanoma and particularly emphasize the potential prognostic value of telomerase reverse transcriptase alterations for these tumors.
Among the canonical cancer-associated genes, only telomerase reverse transcriptase (TERT) promoter mutations were observed in the founding clone in all tumors.