Implementation of TERT promoter mutations improve prognostication of the WHO classification in meningioma

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.

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TERT Promoter Mutations and the 8th Edition TNM Classification in Predicting the Survival of Thyroid Cancer Patients

Cancers ◽

10.3390/cancers13040648 ◽

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.

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Preoperative detection of the TERT promoter mutations in papillary thyroid carcinomas

Clinical Endocrinology ◽

10.1111/cen.14567 ◽

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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Occurrence, functionality, and abundance of the TERT promoter mutations

International Journal of Cancer ◽

10.1002/ijc.33750 ◽

2021 ◽

Author(s):

Sivaramakrishna Rachakonda ◽

Jörg D. Hoheisel ◽

Rajiv Kumar

Keyword(s):

Tert Promoter ◽

Tert Promoter Mutations ◽

Promoter Mutations

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Significance of TERT Genetic Alterations and Telomere Length in Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers13092160 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2160

Author(s):

Jeong-Won Jang ◽

Jin-Seoub Kim ◽

Hye-Seon Kim ◽

Kwon-Yong Tak ◽

Soon-Kyu Lee ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Telomere Length ◽

Differentially Expressed Gene ◽

Genetic Alterations ◽

Tissue Samples ◽

Protein Protein Interaction ◽

Tert Promoter ◽

Tert Promoter Mutations ◽

Promoter Mutations ◽

Tert Expression

Telomerase reverse transcriptase (TERT) mutations are reportedly the most frequent somatic genetic alterations in hepatocellular carcinoma (HCC). An integrative analysis of TERT-telomere signaling during hepatocarcinogenesis is lacking. This study aimed to investigate the clinicopathological association and prognostic value of TERT gene alterations and telomere length in HCC patients undergoing hepatectomy as well as transarterial chemotherapy (TACE). TERT promoter mutation, expression, and telomere length were analyzed by Sanger sequencing and real-time PCR in 305 tissue samples. Protein–protein interaction (PPI) analysis was performed to identify a set of genes that physically interact with TERT. The PPI analysis identified eight key TERT-interacting genes, namely CCT5, TUBA1B, mTOR, RPS6KB1, AKT1, WHAZ, YWHAQ, and TERT. Among these, TERT was the most strongly differentially expressed gene. TERT promoter mutations were more frequent, TERT expression was significantly higher, and telomere length was longer in tumors versus non-tumors. TERT promoter mutations were most frequent in HCV-related HCCs and less frequent in HBV-related HCCs. TERT promoter mutations were associated with higher TERT levels and longer telomere length and were an independent predictor of worse overall survival after hepatectomy. TERT expression was positively correlated with tumor differentiation and stage progression, and independently predicted shorter time to progression after TACE. The TERT-telomere network may have a crucial role in the development and progression of HCC. TERT-telomere abnormalities might serve as useful biomarkers for HCC, but the prognostic values may differ with tumor characteristics and treatment.

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