<i>TERT</i> promoter mutations and polymorphisms as prognostic factors in primary glioblastoma

Mosrati, Mohamed Ali; Malmström, Annika; Łysiak, M; Krysztofiak, A.; Hallbeck, Martin; Milos, Peter; Hallbeck, Anna-Lotta; Bratthäll, Charlotte; Strandéus, Michael; Stenmark-Askmalm, Marie; Söderkvist, Peter

doi:10.18632/oncotarget.4389

Cited by 120 publications

(111 citation statements)

References 47 publications

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“…Specifically, in thyroid cancer, our group and others reported that these mutations are associated with worse prognostic features (age of patients, tumour size and tumour stage), as well as with distant metastases, worse response to treatment and poor survival (Landa et al 2013, Liu et al 2013a,b, Melo et al 2014, George et al 2015, Qasem et al 2015, Nasirden et al 2016. TERT promoter mutations were also associated with shorter survival and/or short disease-free survival in melanomas (Griewank et al 2014, Populo et al 2014, Nagore et al 2016 and glioblastomas (Mosrati et al 2015, Simon et al 2015, Batista et al 2016, Yuan et al 2016.…”

Section: Tert Promoter Mutations In Thyroid Cancermentioning

confidence: 88%

TERT biology and function in cancer: beyond immortalisation

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Vinagre

Sobrinho-Simões

et al. 2017

Journal of Molecular Endocrinology

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Evasion of replicative senescence and proliferation without restriction, sometimes designated as immortalisation, is one of the hallmarks of cancer that may be attained through reactivation of telomerase in somatic cells. In contrast to most normal cells in which there is lack of telomerase activity, upregulation of TERT transcription/activity is detected in 80-90% of malignant tumours. In several types of cancer, there is a relationship between the presence of TERT promoter mutations, TERT mRNA expression and clinicopathological features, but the biological bridge between the occurrence of TERT promoter mutations and the aggressive/invasive features displayed by the tumours remains unidentified. We and others have associated the presence of TERT promoter mutations with metastisation/survival in several types of cancer. In follicular cell-derived thyroid cancer, such mutations are associated with worse prognostic features (age of patients, tumour size and tumour stage) as well as with distant metastases, worse response to treatment and poorer survival. In this review, we analyse the data reported in several studies that imply TERT transcription reactivation/activity with cell proliferation, tumour invasion and metastisation. A particular attention is given to the putative connections between TERT transcriptional reactivation and signalling pathways frequently altered in cancer, such as c-MYC, NF-κB and B-Catenin.

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Section: Tert Promoter Mutations In Thyroid Cancermentioning

confidence: 88%

TERT biology and function in cancer: beyond immortalisation

Pestana

Vinagre

Sobrinho-Simões

et al. 2017

Journal of Molecular Endocrinology

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“…Mutations in the TERT gene are thought to prevent cell senescence through increased telomere length, thus promoting tumorigenesis in several cancers, including GBM (37). The contribution of TERT mutation to tumor aggressiveness however is not clear.…”

Section: Tert Promoter Mutationmentioning

confidence: 99%

“…The contribution of TERT mutation to tumor aggressiveness however is not clear. Focusing on a sample of GBM cases, Mosrati et al found that TERT promoter mutation was associated with a shorter overall survival (37). Interestingly, this mutation was found in both primary and secondary tumors.…”

Section: Tert Promoter Mutationmentioning

confidence: 99%

Molecular Genetics of Secondary Glioblastoma

2017

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Glioblastoma (GBM, WHO grade IV astrocytoma) is among the most common adult brain tumors and one that is invariably fatal. GBM is classified as either primary (de novo) or secondary in origin. Secondary GBMs are derived from previously lower grade (WHO grades II or III) gliomas. While secondary GBMs present with similar clinical characteristics as their primary counterparts, the molecular pathways involved in their pathogenesis distinguish the two and have functional consequences for their behavior. Although a large number of histologic markers are routinely utilized to distinguish primary from secondary GBM, advances in genomic and bioinformatics techniques have drastically improved classification of high-grade gliomas and our understanding of the molecular pathways that influence tumor behavior and response to treatment. The significant influence of molecular identity on tumor behavior has been recognized by the most recent WHO classification of CNS tumors, wherein specific molecular markers have been integrated as part of tumor subtype identification process, as a supplement to traditional histological analysis. Indeed, the change heralds a new era for neuro-oncology, one that is moving toward targeted Genetics of Secondary Glioblastoma 28 therapeutics as part of the standard of care. Thus, a comprehensive grasp of this diverse landscape is necessary. In this chapter, we provide an overview of our latest understanding of the molecular diversity of GBM, specifically as it pertains to primary and secondary GBMs, and how it influences prognostication and therapeutic decision-making.

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“…Glioblastoma multiforme (GBM; World Health Organization grade IV glioma) is the most common type of primary brain tumor worldwide (1). In spite of radical surgery combined with concomitant chemoradiation therapy based on temozolomide, the median survival rate of patients with GBM remains ~1 year (2).…”

Section: Introductionmentioning

confidence: 99%

Preclinical and clinical implications of TERT promoter mutation in glioblastoma multiforme

et al. 2017

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Abstract. The promoter region of the telomerase reverse transcriptase gene (TERT) is mutated in a subpopulation of patients with glioblastoma multiforme (GBM). In the present study, preclinical and clinical implications of the mutation were analyzed in 25 GBMs to evaluate its utility as a therapeutic target. Associations between the TERT promoter mutation and a number of preclinical/clinical characteristics were analyzed. Notably, the TERT promoter mutation was identified in 92.3% of GBMs where dissociated cells revealed in vitro sphere formation capacity; while the TERT promoter mutation was identified in 33.3% of GBMs without in vitro sphere formation capacity (P= 0.004). In addition, this significantly increased mutation rate was observed in GBMs with in vivo tumorigenic potential (80% vs. 0%; P= 0.004). Furthermore, patients with GBM exhibiting the TERT promoter mutation demonstrated significantly decreased overall survival rate compared with patients lacking this mutation (81.7 vs. 152.6 weeks; P=0.026). The results of the present study indicated that the TERT promoter mutation is associated with the self-renewal capacity of GBM cells and clinical aggressiveness of GBMs, which may be translated to a targeting therapy against TERT to inhibit the self-renewal of GBM cells.

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TERT promoter mutations and polymorphisms as prognostic factors in primary glioblastoma

Cited by 120 publications

References 47 publications

TERT biology and function in cancer: beyond immortalisation

TERT biology and function in cancer: beyond immortalisation

Molecular Genetics of Secondary Glioblastoma

Preclinical and clinical implications of TERT promoter mutation in glioblastoma multiforme

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