TERT promoter mutation

Identifying patients with high Ki67 and mutational p53 together with TERT mutations may help predict potential recurrence in aGCT cases.

Our results highlight that the radiological features of bGB are not homogenous and can indicate 2 potential subtypes based on their origins. Further studies are mandatory, but CC-type and Hemispheric-type exhibit distinct clinical backgrounds, outcomes, and molecular features.

TBC1D12 5'UTR mutations were significantly associated with older age at diagnosis (60 vs. 46 for wild type, p = 0.003), pathological T3/T4 stage (85.7% vs. 37.7%, p = 0.010), and advanced tumor stages (85.7% vs. 32.5%, p = 0.006) in PTC. This preliminary study for the first time showed a high prevalence of TBC1D12 5'UTR mutations in ATC and indicated an association between TBC1D12 mutation and aggressive characteristics of PTC, which needs to be confirmed in large cohort studies.

It also discusses the recent advancements in molecular diagnostics, illustrating the promise of TERT mutations as diagnostic tools and prognostic indicators. This review collectively aims to contribute to a deeper understanding of TERT promoter mutations in gliomas, offering a foundation for future research endeavors and paving the way for innovative strategies in glioma management.

In conclusion, PTC in AYA patients differed from PTC in older patients. Particularly, BRAF p.V600E and TERT promoter mutations in AYA with PTC were less frequently observed than in older adults.

One tumor exhibited MSI-High status and a TMB of 19 mut/Mb. Our results indicate the need for further investigation into the role of FOXO1 as a potential prognostic marker in AGCTs.

Nodules with RAS mutations (NRAS, KRAS, HRAS) and TP53 inactivating mutations were considered to be in the intermediate-risk group, while those with non-pathogenic mutations (negative and variants of uncertain significance) were placed in the low-risk group. When combined with cytopathology, NGS increases the sensitivity of diagnosing benign and malignant thyroid nodules, and the reference is useful for patient risk stratification.

DICER1MUT and DICER1WT tumors showed different mRNA expression profiles. The FOXL2 mutation is less common in these tumors and is mutually exclusive with the DICER1 mutation.

Postoperative treatment included radiotherapy and temozolomide...The recurrence was managed with regorafenib and bevacizumab, though complications like hand-foot syndrome and radiation necrosis arose...The novel FGFR3-FASN fusion suggests potential implications for GBM recurrence and lipid metabolism. Further studies are warranted to explore FGFR3-FASN's role in GBM and its therapeutic targeting.

Conclusion In young adult GBM patients, especially those ≤ 40 years of age with long survival, attention should be given to the development of systemic metastases. Metastasis can be the result of multiclonal gene mutations, in which proliferation- and invasion-related gene changes, such as oncogene or tumor suppressor gene mutations and epithelial-mesenchymal transition-related genes, may play an important role in metastasis.

Glioblastoma undergoes heterogeneous genetic, epigenetic, and cellular evolution that underlies prognostically different treatment responses.

In agreement, atypical TERTp mutations co-occur with canonical driver mutations in large cancer cohorts and arise subclonally specifically on the TERTp driver mutant chromosome homolog of melanoma cells treated with UV light in vitro. Our study gives an in-depth view of TERTp mutations in cancer and provides a mechanistic explanation for atypical TERTp mutations.

P2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

This study provides comprehensive genomic profiling of CPTs, highlighting distinct genetic alterations associated with different histological grades and patient demographics. These findings may inform future research and therapeutic strategies targeting specific molecular pathways in CPTs.

Moreover, IDH2 is significantly overexpressed in OCA compared to OA highlighting its potential as a biomarker for differential diagnosis of oncocytic tumors and malignancy. These findings improve the understanding of oncocytic thyroid tumors molecular pathology and suggest IDH2 as a valuable marker for clinical management.

The BRAFV600E and TERT-p double mutation in PTC was significantly associated with relatively old age, larger tumor size, lobulated configuration in tumor margin, papillary excrescences on the cut surface, solid-cut surface, ETE, and high Ki-67 LI. These features are suggestive of the presence of the double mutation and should be analyzed at the molecular level in patients with PTC.

Here, we examine and compare these microfluidic droplet-based methods, exploring their advantages and limitations in liver cancer research. These technologies provide new opportunities to understand liver cancer biology, diagnosis, treatment, and prognosis, contributing to scientific efforts in combating this challenging disease.

TP53 and/or phosphatidylinositol-3 kinase/AKT pathway mutations correlated with overall survival independently of histotype in patients with advanced thyroid cancer. Comprehensive genomic profiling has potential to inform prognosis, as well as identifying treatment targets for patients with advanced thyroid cancer.

Multi-tyrosine kinase inhibitors such as sorafenib and lenvatinib are utilized for treating RAI-refractory FTCs. In addition, given that renin-angiotensin system (RAS) is the most common driver gene for FTC, it is also important to develop RAS inhibitors.

After adjustment for covariates, patients with adult granulosa cell tumors and TERT+ tumors had shorter progression-free survival after first recurrence. TERT promoter mutations may identify a subset of patients with recurrent adult granulosa cell tumors and less favorable outcomes.

Patients with BRAFV600E and TERTp mutations progressed faster to RAIR-DTC than those with BRAFV600E alone (p < 0.01). Our findings suggest that molecular testing for TERTp and other mutations like BRAFV600E may inform early diagnosis, prognosis, and treatment strategies before progression to RAIR-DTC.

In this review, we explore the relative benefits and drawbacks of these computational frameworks and highlight the technical and clinical innovations presented by recent studies in the landscape of fast evolving molecular-based Glioma subtyping. Furthermore, the potential benefits and challenges of incorporating these tools into routine radiological workflows, aiming to enhance patient care and optimize clinical outcomes in the evolving field of CNS tumor management, have been highlighted.

This case introduces a novel fusion partner of MAP3K8 in the context of Spitz melanoma and expands the morphologic and molecular spectrum of Spitz melanoma.

However, they did not affect clinical outcomes, possibly due to short follow-up. Reflex testing for this genetic alteration in miFTCs and miOTCs could be justified regardless of tumor size, though the clinical benefit remains uncertain.

This review summarizes the current knowledge and future perspectives of liquid biopsy of blood and CSF for diagnosis and monitoring of primary CNS tumors.

Our case illustrated that conventional histological and genetic analysis classification can be reclassified according to the DNA methylation analysis, demonstrating that methylation profiling is useful to accurately classify high-grade gliomas, particularly those of the IDH-wildtype subtype.

Molecular analysis revealed a concurrent TERT promoter mutation (C228T) together with the NSD3::NUTM1 fusion, a combination not previously documented in NUT carcinoma. The tumor highlights the need to include NUT carcinoma in the differential diagnosis of thyroid cancer, especially when it presents with unconventional histopathological features, even in the absence of signs of squamous differentiation.

In contrast, all cases tested positive for cytoplasmic β-catenin. RI-refractory PTCs are linked to TERT mutations and exhibit specific aggressive histopathologic features, particularly in tumor centers.

TERT promoter mutations are commonly associated with malignancy, particularly HGCs, when multiple co-occurring molecular alterations are present. However, TERT promoter mutations may occasionally be detected in benign thyroid neoplasms when encountered in isolation or with fewer than 2 additional molecular alterations.

Although the value of preoperative molecular testing for indeterminate nodules (Bethesda III and Bethesda IV) have been analyzed in numerous studies, the impact of preoperative molecular testing on Bethesda V and Bethesda VI thyroid nodules is not adequately described in the current literature. The preoperative recognition of specific molecular mutations, such as BRAFV600E and TERT promoter mutation, might provide more individualized management for thyroid cancer patients by altering the surgical approach and the extent of surgery for patients diagnosed with a more aggressive or iodine-resistant subtype of thyroid cancer.Thyroid cancer is characterized by multiple genetic mutations and alterations and, as a result, preoperative molecular testing of malignant nodules could be a very useful tool for surgeons, enabling them to decide on the most appropriate surgical approach for each patient.

Isolated EIF1AX mutation was noted only in thyroid nodules seen at YNHH and were predominantly encountered in benign thyroid nodules including FND. Accumulation of additional genetic abnormalities appears to be progressively associated with malignant tumors.

Intra- and extrahepatic CCA have distinct clinical and genetic characteristics. Here, we reported a different prevalence of oncogene activating alterations between iCCA and eCCA (e.g., KRAS) that may influence clinical outcome. Moreover, 56 cases had activating alterations (e.g., ERBB2) already targetable in CCA (15% of total cases, 6.2%-eCCA, 20.3%-iCCA) or in other tumours (50% of cases, 81.2%-eCCA, 31.5%-iCCA).

TERT promoter mutation confers sensitivity to PLK1 inhibitors in HCC. The selective growth inhibition of TERT mutant HCC cells induced by PLK1 inhibitor was mediated by Smad3. Combined inhibition of PLK1 and Smad3 showed a cooperative anti-tumor effect in TERT mutant HCC cells.

Dimensions ≥ 4.5 cm (very close to AJCC stage pT3; 9 recurrences, p = 0.041, odd-ratio = 3.7), MPVI (9 recurrences, p = 0.062, OR = 3.3), and TERT (11 recurrences, p = 0.049, OR = 4.4) correlated with disease-free survival also at univariate analysis. The concomitant occurrence of these three variables was present in 7 cases, among which 5 recurred (p = 0.002, OR = 15.94). In conclusion, NGS analysis in resected HCC could not only be used for future therapies but should be integrated with histopathology to predict the risk of tumor recurrence after surgical resection: TERT mutation is among the strongest predictors of tumor recurrence, together with tumor stage (dimensions) and the occurrence of MPVI, which should always be reported separately from the classic MVI.

Coexisting RET/PTC and TERT promoter mutation identify PTC as a unique clinical entity with high mortality, providing new implications for genetic-based prognostication and potential therapeutic targeting of RET and MEK guided by RET/PTC and TERT status.

In summary, only around 50% of WHO 2021 grade 2 meningiomas have an intermediate risk profile. Integrated molecular risk stratification is crucial to guide the management of patients with grade 2 tumors and should be routinely applied to avoid over- and undertreatment, especially concerning the use of adjuvant radiotherapy.

Tyrosine kinase inhibitors i.e, sorafenib and lenvatinib, have been used in cases of progressive, recurrent, or metastatic disease not responsive to 131I therapy. PDTC accounts for 3–5% of all thyroid carcinomas. The 5, 10-, and 15-year survival rates of patients are 50–85%, 34–50%, and 0%, respectively. RAS gene alterations are found in 25–35%, BRAF mutation in 15–27%, TERT promoter mutation in 40% and mutant TP53 in 16–28% of PDTCs.

Case Presentation and We report two cases with RAI-resistant lung metastases treated with larotrectinib: 83-year-old male presenting with an ETV6::NTRK3 fusion-positive tumor with the TERT promoter mutation c.-124C>T, and a 31-year-old female presenting with a TPR::NTRK1 fusion-positive tumor (and negative for TERT promoter mutation)...In contrast, the TERT-negative tumor exhibited successful I-131 reuptake with a TDS of -0.060. As observed for RAI-resistance associated with concurrent TERT and BRAF mutations, the co-occurrence of TERT mutations and NTRK fusions may also contribute to re-sensitization failure.

Multivariate analysis to account for the effect of MGMT promoter methylation and age showed that, in contrast to other published series, this cohort demonstrated improved survival for tumors harboring PTEN mutations, and that there was no observed difference for most other molecular alterations, including EGFR amplification, RB1 loss, or the coexistence of EGFR amplification and deletion/exon skipping (EGFRvIII). Despite limitations in sample size, this study contributes data to the molecular landscape of glioblastomas, prompting further investigations to examine these findings more closely in larger cohorts.

Thus, we recommend performing p16 on all uterine IMTs, which, combined with the risk stratification score, is a promising and cost-effective tool for predicting CDKN2A status and outcome in these patients. It may be particularly useful for tumors with incomplete information for risk stratification (ie, morcellated tumors) and for further stratifying intermediate-risk IMTs when sequencing is unavailable.

Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.

Histopathologic analysis indicated high tumor cell density in FHLs with low ADC. The ADC of FHLs was significantly lower in IDH-wild-type GBM with TERTp mutations, suggesting that determining the ADC of FHLs on preoperative MRI might be helpful in predicting TERTp mutation status and surgical planning.