共查询到20条相似文献,搜索用时 31 毫秒
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Christian Koelsche Marcus Renner Wolfgang Hartmann Regine Brandt Burkhard Lehner Nina Waldburger Ingo Alldinger Thomas Schmitt Gerlinde Egerer Roland Penzel Eva Wardelmann Peter Schirmacher Andreas von Deimling Gunhild Mechtersheimer 《Journal of experimental & clinical cancer research : CR》2014,33(1):33
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Hong Xie Tiantian Liu Na Wang Viveca Bj?rnhagen Anders H??g Catharina Larsson Weng-Onn Lui Dawei Xu 《Oncotarget》2014,5(20):10048-10057
Telomerase activation through the induction of its catalytic component TERT is essential in carcinogenesis. The regulatory mechanism and clinical significance underlying cancer-specific TERT expression have been extensively investigated in various human malignancies, but little is known about these in Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin tumor. Here we addressed these issues by determining TERT promoter mutations, gene amplification, mRNA expression and association with clinical variables in MCC. TERT mRNA was expressed in 6/6 MCC cell lines and 41 of 43 tumors derived from 35 MCC patients. Telomerase activity was detectable in all 6 cell lines and 11 tumors analyzed. TERT promoter mutations were identified in 1/6 cell lines and 4/35 (11.4%) MCC cases. The mutation exhibited UV signature and occurred in sun-exposed areas. Increased TERT gene copy numbers were observed in 1/6 cell lines and 11/14 (79%) tumors, and highly correlated with its mRNA expression (r = 0.7419, P = 0.0024). Shorter overall survival was significantly associated with higher TERT mRNA levels in MCC patients (P = 0.032). Collectively, TERT expression and telomerase activity is widespread in MCC, and may be attributable to TERT promoter mutations and gene amplification. Higher TERT expression predicts poor patient outcomes. 相似文献
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Patrick J. Killela Christopher J. Pirozzi Patrick Healy Zachary J. Reitman Eric Lipp B. Ahmed Rasheed Rui Yang Bill H. Diplas Zhaohui Wang Paula K. Greer Huishan Zhu Catherine Y. Wang Austin B. Carpenter Henry Friedman Allan H. Friedman Stephen T. Keir Jie He Yiping He Roger E. McLendon James E. Herndon II Hai Yan Darell D. Bigner 《Oncotarget》2014,5(6):1515-1525
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Alain Chebly Joana Ropio JeanMarie Peloponese Sandrine Poglio Martina ProchazkovaCarlotti Floriane Cherrier Jacky Ferrer Yamina Idrissi Evelyne SegalBendirdjian Eliane Chouery Chantal Farra Anne PhamLedard Marie BeylotBarry JeanPhilippe Merlio Roland Tomb Edith Chevret 《Molecular oncology》2022,16(9):1931
Cutaneous T‐cell lymphomas (CTCLs) are telomerase‐positive tumors expressing hTERT, although neither gene rearrangement/amplification nor promoter hotspot mutations could explain the hTERT re‐expression. As the hTERT promoter is rich in CpG, we investigated the contribution of epigenetic mechanisms in its re‐expression. We analyzed hTERT promoter methylation status in CTCL cells compared with healthy cells. Gene‐specific methylation analyses revealed a common methylation pattern exclusively in tumor cells. This methylation pattern encompassed a hypermethylated distal region from −650 to −150 bp and a hypomethylated proximal region from −150 to +150 bp. Interestingly, the hypermethylated region matches with the recently named TERT hypermethylated oncogenic region (THOR). THOR has been associated with telomerase reactivation in many cancers, but it has so far not been reported in cutaneous lymphomas. Additionally, we assessed the effect of THOR on two histone deacetylase inhibitors (HDACi), romidepsin and vorinostat, both approved for CTCL treatment and a DNA methyltransferase inhibitor (DNMTi) 5‐azacytidine, unapproved for CTCL. Contrary to our expectations, the findings reported herein revealed that THOR methylation is relatively stable under these epigenetic drugs'' pressure, whereas these drugs reduced the hTERT gene expression. 相似文献
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Masayuki Yoshida Reiko Ogawa Hiroshi Yoshida Akiko Maeshima Yae Kanai Takayuki Kinoshita Nobuyoshi Hiraoka Shigeki Sekine 《British journal of cancer》2015,113(8):1244-1248
Background:
Phyllodes tumors are rare fibroepithelial neoplasms of the breast, which carry the potential risk of local recurrence and metastasis. Phyllodes tumors share several histological features with fibroadenomas, and no widely accepted markers for distinguishing these lesions have been identified.Methods:
We analyzed molecular abnormalities related to telomere elongation in tumors, including TERT promoter mutations, as well as loss of expression of ATRX and DAXX, in a total of 104 phyllodes tumors and fibroadenomas.Results:
Sequencing analyses showed that TERT promoter mutations were frequent in phyllodes tumors (30/46, 65%), but rare in fibroadenomas (4/58, 7%). Among phyllodes tumors, the mutations were more frequent in borderline tumors (13/15, 87%), but were also common in benign (9/18, 50%) and malignant tumors (8/13, 62%). Remarkably, all but one TERT promoter-mutated tumor also contained MED12 mutations, indicating that these mutations are strongly associated (P=8.4 × 10−6). Expression of ATRX and DAXX, as evaluated by immunohistochemistry, was retained in all tumors.Conclusions:
Our observations suggest a critical role of TERT promoter mutations, in cooperation with MED12 mutations, in the development of phyllodes tumors. Because TERT promoter mutations are rare among fibroadenomas, their detection may be of potential use in discriminating between phyllodes tumors and fibroadenomas. 相似文献13.
Ricardo Leão Donghyun Lee Arnaldo Figueiredo Thomas Hermanns Peter Wild Martin Komosa Irene Lau Mathew Mistry Nuno Miguel Nunes Aryeh J. Price Cindy Zhang Tatiana Lipman Cédric Poyet Nadejda Valtcheva Kathrin Oehl Hugo Coelho Rashid Sayyid Ana Melo Gomes Ligia Prado e Castro Joan Sweet João Vinagre Joana Apolónio Derek Stephens Inês Faleiro Kamel Fadaak Patrick O. Richard Girish Kulkarni Alexandre R. Zlotta Robert J. Hamilton Pedro Castelo-Branco Uri Tabori 《International journal of cancer. Journal international du cancer》2019,144(7):1676-1684
In urothelial bladder cancer (UBC), risk stratification remains an important unmet need. Limitless self-renewal, governed by TERT expression and telomerase activation, is crucial for cancer progression. Thus, telomerase activation through the interplay of mutations (TERTpMut) and epigenetic alterations in the TERT promoter may provide further insight into UBC behavior. Here, we investigated the combined effect of TERTpMut and the TERT Hypermethylated Oncological Region (THOR) status on telomerase activation and patient outcome in a UBC international cohort (n = 237). We verified that TERTpMut were frequent (76.8%) and present in all stages and grades of UBC. Hypermethylation of THOR was associated with higher TERT expression and higher-risk disease in nonmuscle invasive bladder cancers (NMIBC). TERTpMut alone predicted disease recurrence (HR: 3.18, 95%CI 1.84 to 5.51, p < 0.0001) but not progression in NMIBC. Combined THORhigh/TERTpMut increased the risk of disease recurrence (HR 5.12, p < 0.0001) and progression (HR 3.92, p = 0.025). Increased THOR hypermethylation doubled the risk of stage progression of both TERTpwt and TERTpMut NMIBC. These results highlight that both mechanisms are common and coexist in bladder cancer and while TERTpMut is an early event in bladder carcinogenesis THOR hypermethylation is a dynamic process that contributes to disease progression. While the absence of alterations comprises an extremely indolent phenotype, the combined genetic and epigenetic alterations of TERT bring additional prognostic value in NMIBC and provide a novel insight into telomere biology in cancer. 相似文献
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Distinct profiles of TERT promoter mutations and telomerase expression in head and neck cancer and cervical carcinoma
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Stefano Greggi Franco Ionna Simona Losito Gerardo Botti Luigi Buonaguro Franco M. Buonaguro Maria Lina Tornesello 《International journal of cancer. Journal international du cancer》2018,143(5):1153-1161
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The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism
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Joana Peixoto Telmo A. Catarino Nathalia Cristina Campanella Weder Menezes Aline Paixão Becker Gisele Caravina de Almeida Marcus M. Matsushita Carlos Clara Luciano Neder Marta Viana‐Pereira Mrinalini Honavar Lígia Castro José Manuel Lopes Bruno Carvalho Rui Manuel Vaz Valdemar Máximo Paula Soares Manuel Sobrinho‐Simões Rui Manuel Reis Jorge Lima 《International journal of cancer. Journal international du cancer》2016,139(2):414-423
Human hotspot TERT promoter (TERTp) mutations have been reported in a wide range of tumours. Several studies have shown that TERTp mutations are associated with clinicopathological features; in some instances, TERTp mutations were considered as biomarkers of poor prognosis. The rs2853669 SNP, located in the TERT promoter region, was reported to modulate the increased TERT expression levels induced by the recurrent somatic mutations. In this study we aimed to determine the frequency and prognostic value of TERTp mutations and TERT rs2853669 SNP in 504 gliomas from Portuguese and Brazilian patients. TERTp mutations were detected in 47.8% of gliomas (216/452). Glioblastomas (GBM) exhibited the highest frequency of TERTp mutations (66.9%); in this glioma subtype, we found a significant association between TERTp mutations and poor prognosis, regardless of the population. Moreover, in a multivariate analysis, TERTp mutations were the only independent prognostic factor. Our data also showed that the poor prognosis conferred by TERTp mutations was restricted to GBM patients carrying the rs2853669 A allele and not in those carrying the G allele. In conclusion, the presence of TERTp mutations was associated with worse prognosis in GBM patients, although such association depended on the status of the rs2853669 SNP. The status of the rs2853669 SNP should be taken in consideration when assessing the prognostic value of TERTp mutations in GBM patients. TERTp mutations and the rs2853669 SNP can be used in the future as biomarkers of glioma prognosis. 相似文献
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Sívaramakrishna Rachakonda Zaida Garcia‐Casado Celia Requena Virtudes Soriano Christoph Frank Victor Traves Esther Quecedo Josefa Sanjuan‐Gimenez Kari Hemminki Maria Teresa Landi Rajiv Kumar 《International journal of cancer. Journal international du cancer》2016,139(1):75-84
Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at‐risk primary melanoma patients. In this study, we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. Tumors from 300 patients with stage I/II melanoma were sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression‐free and melanoma‐specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease‐free and melanoma‐specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease‐free survival was 2.3 (95% CI 1.2–4.4) and for melanoma‐specific survival 5.8 (95% CI 1.9–18.3). The effect of the mutations on melanoma‐specific survival in noncarriers of variant allele of the polymorphism was significant (HR 4.5, 95% CI 1.4–15.2) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.3, 95% CI 0.1–0.9). The data in this study provide preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter. 相似文献
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CTCF mediates the TERT enhancer–promoter interactions in lung cancer cells: Identification of a novel enhancer region involved in the regulation of TERT gene
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Vegard Eldholm Aage Haugen Shanbeh Zienolddiny 《International journal of cancer. Journal international du cancer》2014,134(10):2305-2313
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Hiroyuki Seimiya 《Cancer science》2020,111(9):3089-3099