TERT mutation

P=N/A, N=500, Southwest Hospital; Southwest Hospital

In the IDH-mutant subgroup, it tended to co-occur with CIC and FUBP1 alterations, while being mutually exclusive with ATRX and TP53 alterations. These correlations may further refine prognostic predictions.

In conclusion, TERT mutations in biliary tract carcinomas had unique clinicopathologic and genetic characteristics. Despite its poor PFS, the concomitant presence of ERBB2 amplification and a high TMB indicated a potential for targeted therapy and immunotherapy in this specific subtype.

We highlight the promising results of the clinical trial involving the combination of adavosertib and irinotecan, which encourages further clinical trials with adavosertib targeting NB with ATRX mutations. Preclinical results with BET inhibitors (OTX015 and AZD5153) and with 6-thio-2'-deoxyguanosine, targeting NB with TERT mutations, are promising. Both represent future therapeutic targets, emphasizing the need to prioritize research using these models.

SGCs are a heterogeneous group of malignancies with distinct molecular landscape that characterized by poor prognosis and inadequate treatment options. Nonstandard strategies might be beneficial for patients who suffer from salivary gland cancers. Wider utilization of NGS analysis may increase the opportunity for patients with those rare cancers to receive more precise, personalized therapy.

The results of our study further support the hypothesis that the pathogenesis of JGCT may be driven by activation of the PIK3/AKT/mTOR pathway. These findings could potentially have future therapeutic implications, as treatment strategies targeting the PTEN/mTOR pathways are currently under investigation.

The FOXL2 missense mutation was the only common somatic DNA alteration in aGCT. TERT promoter mutations were reported more frequently in recurrent aGCT but their clinical relevance remains uncertain. In contrast to previous reports, truncating KMT2D mutations were not found to be associated with recurrent aGCT. Evidence on common germline variants in aGCT is sparse. The role of somatic and germline DNA alterations in the development of other malignancies in women with aGCT remains uncertain. Further research involving matched primary and recurrent tumors, as well as other primary malignancies, is essential to better understand the mutations that drive tumor development.

ADC histogram analysis may be a potential noninvasive biomarker for differentiating MGMT and TERT molecular markers and providing prognostic information for GBM patients.

The released CCL13 enhances the infiltration of T cells within the tumor, potentially contributing to the improved prognosis observed in patients with high p16INK4A expression. These findings suggest that tumor cells with a senescence phenotype in GBM, through the secretion of chemokines such as CCL13, may augment immune cell infiltration and potentially enhance patient outcomes by creating a more immunologically active tumor microenvironment.

A review of previously reported cases confirmed as Spitz melanoma with distant metastases (n = 7) revealed a broad age range (11-71 years, median 46 years), high mortality (5/7), frequent BRAF fusions (6/7), and recurrent TERT promotor mutations and CDKN2A/B deletions. This report adds valuable insights into our understanding of the clinical and genetic characteristics of Spitz melanoma with distant metastases.

BRAFmutpTERTwt had higher stromal lymphocytes infiltration as compared to BRAFwtpTERTwt tumors, corroborating the transcriptomic findings. To our knowledge this is the first report of a potential link between TERT and the immune microenvironment, offering an explanation for the aggressive nature of BRAFmutpTERTmut PTC.