Telomerase Reverse Transcriptase Gene Promoter Mutations Help Discern the Origin of Urogenital Tumors: A Genomic and Molecular Study

Wu, Song; Huang, Peide; Li, Chong; Huang, Yi; Li, Xianxin; Wang, Yongqiang; Chen, Chao; Lv, Zhaojie; Tang, Aifa; Sun, Xiaojuan; Lu, Jingxiao; Li, Weiping; Zhou, Jie; Gui, Yaoting; Zhou, Fangjian; Wang, Daping; Cai, Zhiming

doi:10.1016/j.eururo.2013.10.038

Cited by 87 publications

(107 citation statements)

References 7 publications

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“…Similar to cell lines, the same TERT promoter mutations were detected frequently in BC, with a prevalence ranging from 47 to 85 % (Table 2) [1,54,61,77,99,121,125]. These results rank TERT promoter mutations as one of the most frequent genomic events, possibly the most frequent, in BC [1,54,61,77,99,121,125]. TERT mutations were significantly more frequent among FGFR3 mutant tumours [1].…”

Section: Telomerase Promoter Mutations In Bladder Carcinomassupporting

confidence: 58%

“…Conflicting results have been reported on the association between TERT promoter mutations and clinical stage and/or grade of bladder tumours. Wu and colleagues found that TERT promoter mutations are more prevalent in muscle invasive (MI) than in non-muscle invasive (NMI) tumours and also more prevalent in BC patients with advanced tumour stages (T2-4) than in those with low stage tumours (Ta or T1) [125]. At variance with this, another report found no association between mutation status and stage or grade of BC [54].…”

Section: Telomerase Promoter Mutations In Bladder Carcinomasmentioning

confidence: 55%

“…TERT mutations were significantly more frequent among FGFR3 mutant tumours [1]. Wu and colleagues reported a significant co-occurrence of TERT promoter mutations and TP53/RB1 inactivating somatic mutations [125] indicating that both mutations may cooperatively contribute to the progression of BC [125]. Conflicting results have been reported on the association between TERT promoter mutations and clinical stage and/or grade of bladder tumours.…”

Section: Telomerase Promoter Mutations In Bladder Carcinomasmentioning

confidence: 55%

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Telomerase promoter mutations in cancer: an emerging molecular biomarker?

et al. 2014

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Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the "alternative mechanism of telomere lengthening" (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and nonneoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target.

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Section: Telomerase Promoter Mutations In Bladder Carcinomassupporting

confidence: 58%

Section: Telomerase Promoter Mutations In Bladder Carcinomasmentioning

confidence: 55%

Section: Telomerase Promoter Mutations In Bladder Carcinomasmentioning

confidence: 55%

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Telomerase promoter mutations in cancer: an emerging molecular biomarker?

et al. 2014

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“…The correlation between TERT promoter mutations and older patient age has been shown in glioblastoma, medulloblastoma, 20 papillary thyroid carcinoma (445 years old), 27 and urothelial carcinoma of the urinary bladder (450 years old). 28 In contrast, a previous study by Wu et al showed that no relationship could be found between patient age and TERT promoter mutations. 21 This discrepancy may be the result of different statistical methodologies and different patient cohorts.…”

Section: Discussionmentioning

confidence: 87%

“…In primary glioblastomas, 20 differentiated thyroid carcinomas 30 and urothelial carcinomas of the urinary bladder, 28 TERT promoter mutation was an indicator of poor clinical outcome. In ovarian clear cell carcinomas, Widschwendter et al 15 and Wu et al 21 reported that TERT expression and TERT promoter mutation revealed no prognostic impact.…”

Section: Discussionmentioning

confidence: 99%

Molecular alterations in endometrial and ovarian clear cell carcinomas: clinical impacts of telomerase reverse transcriptase promoter mutation

et al. 2015

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Recently, mutations of telomerase reverse transcriptase (TERT) promoter were found in several types of cancer. A few reports demonstrate TERT promoter mutations in ovarian clear cell carcinomas but endometrial clear cell carcinoma has not been studied. The aims of this study were to compare differences of molecular alterations and clinical factors, and identify their prognostic impact in endometrial and ovarian clear cell carcinomas. We evaluated mutations of the TERT promoter and PIK3CA, expression of ARID1A, and other clinicopathological factors in 56 ovarian and 14 endometrial clear cell carcinomas. We found that TERT promoter mutations were present in 21% (3/14) of endometrial clear cell carcinomas and 16% (9/56) of ovarian clear cell carcinomas. Compared with ovarian clear cell carcinomas, endometrial clear cell carcinomas showed older mean patient age (Po0.001), preserved ARID1A immunoreactivity (P ¼ 0.017) and infrequent PIK3CA mutation (P ¼ 0.025). In ovarian clear cell carcinomas, TERT promoter mutations were correlated with patient age 445 (P ¼ 0.045) and preserved ARID1A expression (P ¼ 0.003). In cases of endometrial clear cell carcinoma, TERT promoter mutations were not statistically associated with any other clinicopathological factors. In ovarian clear cell carcinoma patients with early FIGO stage (stages I and II), TERT promoter mutation was an independent prognostic factor and correlated with a shorter disease-free survival and overall survival (P ¼ 0.015 and 0.009, respectively). In recurrent ovarian clear cell carcinoma patients with early FIGO stage, TERT promoter mutations were associated with early relapse within 6 months (P ¼ 0.018). We concluded that TERT promoter mutations were present in endometrial and ovarian clear cell carcinomas. Distinct molecular alteration patterns in endometrial and ovarian clear cell carcinomas implied different processes of tumorigenesis in these morphologically similar tumors. In ovarian clear cell carcinoma of early FIGO stage, patients with TERT promoter mutation require close follow-up during the initial 6 months following chemotherapy. Modern Pathology (2015) 28, 303-311; doi:10.1038/modpathol.2014 published online 1 August 2014 Ovarian clear cell carcinoma represents 5-25% of all epithelial ovarian carcinomas with geographic variation. 1 Compared with high-grade serous adenocarcinomas, ovarian clear cell carcinomas are characterized by a higher incidence among Asians, younger patient age and early tumor staging at presentation, association with endometriosis, higher frequencies of AT-rich interactive domain 1 A (ARID1A) mutation and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation, and higher resistance to first-line platinum and taxane-based chemotherapy.

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Hope and challenge: Precision medicine in bladder cancer

Jiang

Tao

et al. 2019

Cancer Medicine

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Bladder cancer (BC) is a complex disease and could be classified into nonmuscle‐invasive BC (NMIBC) or muscle‐invasive BC (MIBC) subtypes according to the distinct genetic background and clinical prognosis. Until now, the golden standard and confirmed diagnosis of BC is cystoscopy and the major problems of BC are the high rate of recurrence and high costs in the clinic. Recent molecular and genetic studies have provided perspectives on the novel biomarkers and potential therapeutic targets of BC. In this article, we provided an overview of the traditional diagnostic approaches of BC, and introduced some new imaging, endoscopic, and immunological diagnostic technology in the accurate diagnosis of BC. Meanwhile, the minimally invasive precision treatment technique, immunotherapy, chemotherapy, gene therapy, and targeted therapy of BC were also included. Here, we will overview the diagnosis and therapy methods of BC used in clinical practice, focusing on their specificity, efficiency, and safety. On the basis of the discussion of the benefits of precision medicine in BC, we will also discuss the challenges and limitations facing the non‐invasive methods of diagnosis and precision therapy of BC. The molecularly targeted and immunotherapeutic approaches, and gene therapy methods to BC treatment improved the prognosis and overall survival of BC patients.

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Telomerase Reverse Transcriptase Gene Promoter Mutations Help Discern the Origin of Urogenital Tumors: A Genomic and Molecular Study

Cited by 87 publications

References 7 publications

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

Molecular alterations in endometrial and ovarian clear cell carcinomas: clinical impacts of telomerase reverse transcriptase promoter mutation

Hope and challenge: Precision medicine in bladder cancer

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