Association of Telomerase Reverse Transcriptase Promoter Mutations with the Prognosis of Glioma Patients: a Meta-Analysis

Wang, Xiaogang; Li, Xiaoming; Xu, Feng; Zhang, Youqian; Liu, Hongwei; Tao, Yingqun

doi:10.1007/s12035-015-9400-2

Cited by 12 publications

(10 citation statements)

References 39 publications

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“…In neuroblastoma, tumors without detectable TERT mRNA frequently undergo spontaneous regression [93], whereas TERT expression, and/or its gene amplification or rearrangements are closely associated with a highrisk/aggressive disease and shorter survival [71][72][73]. The presence of TERT promoter mutations has recently been shown as a unfavorable prognostic factor in a number of cancer types including papillary thyroid carcinoma, glioblastoma, bladder cancer, and others [31,[94][95][96][97]. In addition, the association between TERT promoter hypermehtylation and poor outcomes or progression was reported in brain tumors and adrenocortical carcinoma [25,98].…”

Section: Outcome Predictionmentioning

confidence: 99%

Mechanisms underlying the activation of TERT transcription and telomerase activity in human cancer: old actors and new players

2019

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Long-lived species Homo sapiens have evolved robust protection mechanisms against cancer by repressing telomerase and maintaining short telomeres, thereby delaying the onset of the majority of cancer types until post-reproductive age. Indeed, telomerase is silent in most differentiated human cells, predominantly due to the transcriptional repression of its catalytic component telomerase reverse transcriptase (TERT) gene. The lack of telomerase/TERT expression leads to progressive telomere erosion in dividing human cells, whereas critically shortened telomere length induces a permanent growth arrest stage named replicative senescence. TERT/telomerase activation has been experimentally shown to be essential to cellular immortalization and malignant transformation by stabilizing telomere length and erasing the senescence barrier. Consistently, TERT expression/telomerase activity is detectable in up to 90% of human primary cancers. Compelling evidence has also accumulated that TERT contributes to cancer development and progression via multiple activities beyond its canonical telomere-lengthening function. Given these key roles of telomerase and TERT in oncogenesis, great efforts have been made to decipher mechanisms underlying telomerase activation and TERT induction. In the last two decades since the TERT gene and promoter were cloned, the derepression of the TERT gene has been shown to be achieved typically at a transcriptional level through dysregulation of oncogenic factors or signaling, post-transcriptional/translational regulation and genomic amplification. However, advances in high-throughput next-generation sequencing technologies have prompted a revolution in cancer genomics, which leads to the recent discovery that genomic alterations take center stage in activating the TERT gene. In this review article, we summarize critical mechanisms activating TERT transcription, with special emphases on the contribution of TERT promoter mutations and structural alterations at the TERT locus, and briefly discuss the underlying implications of these genomic events-driven TERT hyperactivity in cancer initiation/progression and potential clinical applications as well.

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Section: Outcome Predictionmentioning

confidence: 99%

Mechanisms underlying the activation of TERT transcription and telomerase activity in human cancer: old actors and new players

2019

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“…Ao passo em que Fan et al 39 não encontraram relação, Wang et al 50 , em seu artigo "The TERT promoter mutation status and MGMT promoter methylation status, combined with dichotomized MRI-derived and clinical features, predict adult primary glioblastoma survival" 50 , mostraram haver uma relação presente. Primeiramente, a comparação entre tumores com e sem a mutação do promotor mostrou a presença de edema peritumoral duas vezes maior nos tumores com a mutação onde as relações entre os biomarcadores moleculares e características relacionadas ao GBM primário em adultos.…”

Section: Resultsunclassified

“…Na figura 1 vemos a relação da sobrevida com o edema peritumoral e a mutação do promotor, presente no artigo de Wang et al 50 Figura 1. Relação da sobrevida entre edema peritumoral e mutação do promotor 50 No artigo de Wang et al 50 os resultados permitem predizer que pacientes com intenso edema peritumoral, detectado através de imagens de ressonância magnética, e com a mutação do promotor do TERT presente, detectado pós-cirurgicamente no tecido tumoral, terão pior prognóstico e uma maior mortalidade.…”

Section: Resultsunclassified

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Valor Prognóstico da Mutação do Promotor do TERT e sua Correlação com o Aumento do Edema Peritumoral em Pacientes com Glioblastomas

Martinez¹,

Aguiar²,

Gois³

et al. 2020

jbnc

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Introdução: O glioblastoma constitui o tumor maligno primário do sistema nervoso central mais comum do indivíduo adulto do sexo masculino. Asobrevida média dos doentes com glioblastoma é de 3 a 5 meses sem tratamento, e na adoção de tratamento cirúrgico associado a quimioterapia eradioterapia a sobrevida pode chegar entre 9 a 15 meses. Marcadores de prognóstico devem ser testados e validados almejando a adequada estratificaçãoterapêutica destes pacientes e, consequentemente, o seu prognóstico. Objetivo: Revisão sistemática que visa estudar a mutação da transcriptase reversada telomerase em gliomas de alto grau, avaliando sua correlação com o prognóstico e a formação de edema peritumoral. Métodos: A partir da basede dados on-line do PubMed foram levantados artigos que mostrassem relação com gliomas de alto grau, mutação do promotor TERT ou edemaperitumoral em glioblastomas. Trinta artigos foram escolhidos para serem analisados mais detalhadamente. Foram escolhidos artigos de 2008 a 2018,com n de pelo menos 126. O fator de impacto considerado foi de > 1,0 ponto. Todos os artigos selecionados estavam em inglês. Cada artigo foi estudadoe os resultados importantes obtidos foram descritos em nossos próprios resultados. Resultados: A partir da análise de 30 artigos, em 43,3% delespôde-se constatar uma relação de menor sobrevida com a presença da mutação do promotor do TERT. Além disso, 16,6% mostraram a presença damutação como mais prevalente em glioblastomas primários. A relação entre a mutação e a formação do edema foi inconclusiva. Na literatura levantada,houve divergência, sendo que metade afirmou não haver relação significante, enquanto que a outra metade mostrou que a mutação leva à formaçãoaumentada do edema peritumoral. Conclusão: Conclui-se maior necessidade de estudos e pesquisas relacionando a mutação do promotor do TERTcom a formação do edema peritumoral, pois a literatura é escassa sobre o tema, visto que ser recente o início das pesquisas com os biomarcadorestumorais. Este incremento pode trazer importante informação prognóstica, além de possibilitar novos métodos de tratamento específico e guiado.

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“…Furthermore, in cancer cells, TERT upregulation can be achieved by TERT amplifications, TERT promoter mutations, and TERT promoter methylation [ 94 , 95 ]. In gliomas, the prevalence of mutations on the TERT promoter is remarkably high in primary GBMs (approximately 80%) ( Figure 3 A) [ 96 ], and recent evidence suggested the presence of TERT promoter mutations as an unfavorable prognostic factor in GBM [ 97 ]. Recurrent non-coding point mutations within the TERT promoter are predominantly observed at two nucleotide positions: −124 and −146 bp upstream from the ATG, denoted C228T and C250T, respectively [ 98 ].…”

Section: Molecular Pathogenesis Of Gbmmentioning

confidence: 99%

Present and Future of Anti-Glioblastoma Therapies: A Deep Look into Molecular Dependencies/Features

Kim

2020

Molecules

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Glioblastoma (GBM) is aggressive malignant tumor residing within the central nervous system. Although the standard treatment options, consisting of surgical resection followed by combined radiochemotherapy, have long been established for patients with GBM, the prognosis is still poor. Despite recent advances in diagnosis, surgical techniques, and therapeutic approaches, the increased patient survival after such interventions is still sub-optimal. The unique characteristics of GBM, including highly infiltrative nature, hard-to-access location (mainly due to the existence of the blood brain barrier), frequent and rapid recurrence, and multiple drug resistance mechanisms, pose challenges to the development of an effective treatment. To overcome current limitations on GBM therapy and devise ideal therapeutic strategies, efforts should focus on an improved molecular understanding of GBM pathogenesis. In this review, we summarize the molecular basis for the development and progression of GBM as well as some emerging therapeutic approaches.

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Association of Telomerase Reverse Transcriptase Promoter Mutations with the Prognosis of Glioma Patients: a Meta-Analysis

Cited by 12 publications

References 39 publications

Mechanisms underlying the activation of TERT transcription and telomerase activity in human cancer: old actors and new players

Mechanisms underlying the activation of TERT transcription and telomerase activity in human cancer: old actors and new players

Valor Prognóstico da Mutação do Promotor do TERT e sua Correlação com o Aumento do Edema Peritumoral em Pacientes com Glioblastomas

Present and Future of Anti-Glioblastoma Therapies: A Deep Look into Molecular Dependencies/Features

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