Comparative study of TERT
 promoter mutation status within spatially, temporally and morphologically distinct components of urothelial carcinoma

353 Background: Currently, there are no FDA-approved blood biomarkers for the prognosis or prediction of outcomes in urothelial carcinoma (UC). The telomerase reverse transcriptase ( TERT) promoter is recurrently mutated at high frequency in UC (50%). These mutations have been correlated with tumor recurrence and survival. Tumor cell-free DNA (cfDNA) with somatic genomic alterations can be found in the plasma of cancer patients and has the potential for use as a non-invasive cancer biomarker. Detection of TERT promoter mutations in cfDNA might be used as a prognostic tool to monitor disease outcome in UC patients. We set out to detect tumor cfDNA and TERT promoter mutations in cfDNA from patients with UC at different stages. Methods: UC patients receiving chemotherapy in the neoadjuvant, first or second-line metastatic setting had blood collected either before or during therapy. cfDNA was isolated from ~1ml plasma samples using the QIAmp (Qiagen) kit. Samples underwent ultra-low pass whole genome sequencing (ULP-WGS) to determine whether tumor cfDNA could be detected in these samples. TERT promoter mutations were detected using a sensitive qPCR assay. Results: 40 plasma samples from a total of 32 patients with urothelial carcinoma were analyzed. Sufficient amounts of plasma cfDNA were obtained for library construction and ULP-WGS in 11 patients. 6 of these 11 patients were determined to be positive for detectable tumor cfDNA and of these, all were metastatic and 50% (3/6) were positive for a TERT promoter mutation. In total, 8 out of 40 samples (20%) were positive for a TERT promoter mutation, including samples from two patients where total cfDNA yield was insufficient for library construction. A total of ~20% of patients with metastatic disease were positive for TERT promoter mutations in cfDNA. The low percentage of samples having sufficient cfDNA most likely reflects the low volume of plasma used. Conclusions: TERT promoter mutations were identified in cfDNA of UC patients. ULP-WGS showed tumor cfDNA in patients with a high tumor burden and metastatic disease. TERTpromoter mutations in cfDNA could potentially be used as a non-invasive method for detection of disease. These results have implications for the use of cfDNA in the evaluation of advanced UC.

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TERT Promoter Mutation Status as an Independent Prognostic Factor in Cutaneous Melanoma

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/dju246 ◽

2014 ◽

Vol 106 (9) ◽

Cited By ~ 132

Author(s):

Klaus G. Griewank ◽

Rajmohan Murali ◽

Joan Anton Puig-Butille ◽

Bastian Schilling ◽

Elisabeth Livingstone ◽

...

Keyword(s):

Prognostic Factor ◽

Cutaneous Melanoma ◽

Independent Prognostic Factor ◽

Tert Promoter Mutation ◽

Promoter Mutation ◽

Mutation Status ◽

Tert Promoter

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TERT promoter mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic glioma with molecular features of glioblastoma

Acta Neuropathologica ◽

10.1007/s00401-021-02337-9 ◽

2021 ◽

Author(s):

Kenji Fujimoto ◽

Hideyuki Arita ◽

Kaishi Satomi ◽

Kai Yamasaki ◽

Yuko Matsushita ◽

...

Keyword(s):

Tert Promoter Mutation ◽

Promoter Mutation ◽

Mutation Status ◽

Astrocytic Glioma ◽

Molecular Features ◽

Tert Promoter ◽

Necessary And Sufficient

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Faculty Opinions recommendation of TERT promoter mutation status as an independent prognostic factor in cutaneous melanoma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718874226.793519576 ◽

2016 ◽

Author(s):

Iwei Yeh

Keyword(s):

Prognostic Factor ◽

Cutaneous Melanoma ◽

Independent Prognostic Factor ◽

Tert Promoter Mutation ◽

Promoter Mutation ◽

Mutation Status ◽

Tert Promoter

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Effect of ARMS-qPCR on detection sensitivity of earlier diagnosis of papillary thyroid cancers with worse prognosis determined by BRAF V600E and TERT promoter mutation coexisting.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.6588 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 6588-6588

Author(s):

Peng-cheng Yu ◽

Li-cheng Tan ◽

Xiao Shi ◽

Ben Ma ◽

Wen-jun Wei ◽

...

Keyword(s):

Thyroid Cancer ◽

Recurrence Rate ◽

Braf V600e ◽

Tert Promoter Mutation ◽

Papillary Thyroid ◽

Promoter Mutation ◽

Mutation Status ◽

Tert Promoter ◽

Worse Prognosis ◽

Sensitive Method

6588 Background: Co-existing of BRAF V600E and TERT promoter C228T/C250T mutation has been extensively related to prognosis in thyroid cancer. Our study aimed to establish a more sensitive method for mutation detection and explore the correlation more in-depth. Methods: BRAF and TERT promoter mutation status of 250 papillary thyroid cancer was detected by both Amplification Refractory Mutation System quantitative PCR (ARMS-qPCR) and Sanger sequencing to compare the sensitivity. The associations between the mutation status and the clinicopathological features were analyzed. Results: ARMS-qPCR displayed higher sensitivity than Sanger ( BRAF V600E: 75.2% vs. 52.4%, p< 0.001; TERT promoter C228T/C250T: 12.0% vs. 3.6%, p= 0.001; Co-mutation (9.6% vs. 3.2%, p= 0.005). Both methods indicated that patients with BRAF V600E and TERT promoter co-mutation were higher in age at diagnosis (ARMS-qPCR: 51.0 ± 14.2 vs. 40.2 ± 12.6, p <0.001; Sanger: 64.3 ± 7.1 vs. 40.5 ± 12.6, p <0.001), and the recurrence rate (16.7% vs. 3.1%, p= 0.014; 50.0% vs. 2.9%, p< 0.001), besides, the co-mutation group were related to more advanced TNM stage ( p< 0.001; p< 0.001) and higher MACIS score (5.1 ± 1.5 vs. 4.2 ± 0.7, p= 0.006; 6.6 ± 1.1 vs. 4.2 ± 0.8, p< 0.001). In addition, compared with the co-mutation results of Sanger, it seems that ARMS-qPCR has identified an earlier stage of group, which were younger (43.3 ± 10.1 vs. 66.4 ± 6.1, p< 0.001), and with smaller tumor (1.8 ± 1.5 vs. 4.0 ± 1.3, p= 0.002), as well as lower recurrence rate ( 0.0% vs. 50%, p= 0.007). Besides, the newly identified group were lower in MACIS score (4.2 ± 0.8 vs. 6.9 ± 0.7, p= 0.002) and with lower TNM stage ( p= 0.001). Conclusions: Patients with BRAF V600E and TERT promoter C228T/C250T co-mutation have a worse prognosis. Using ARMS-qPCR, the more sensitive method could identify earlier stages of patients with a potentially worse prognosis. [Table: see text]

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