Clinical implications of quantitative real-time RT–PCR analysis of hTERT gene expression in human gliomas

Abstract

The presence of telomerase activity in a glioma may be a predictor of its malignant potential. Activation of telomerase is regulated at the transcriptional level of the human telomerase reverse transcriptase (hTERT). Here, we evaluated whether the amount of hTERT mRNA provides a molecular marker of glioma malignancy that would have clinical utility. We used a real-time RT -PCR to assess the number of hTERT transcripts in primary tumour samples derived from 70 glioma patients. Results were standardised by quantifying the number of ABL transcripts as internal control and expressed as hTERT/ABL ratio. The percentage of patients with detectable hTERT mRNA markedly increased with enhanced malignancy: low-grade gliomas expressed hTERT in one out of 14 cases (7.1%), anaplastic gliomas in four out of 13 cases (30.8%) and glioblastoma multiforme (GBM) tumours in 30 out of 43 cases (69.8%). The mean hTERT/ABL ratio was significantly higher in GBMs than in non-GBMs. Subdividing hTERT/ABL ratios as low (p25%) and high (425%), we found that the overall survival among hTERT-positive GBMs was significantly worse in high hTERT expressors than in low hTERT expressors (P ¼ 0.0082). We conclude that the amount of hTERT mRNA may represent a diagnostic and prognostic indicator for GBM patients.

mRNA quantification and clinical evaluation of telomerase reverse transcriptase subunit (hTERT) in intracranial tumours of patients in the island of Crete

“…Similar results have been reported from other authors. Tchirkov et al (2003), using the same method, reported hTERT mRNA-positive expression in 69.8% of glioblastoma multiforme samples, when in the present study we found 66.6%. Kleinschmidt-DeMasters et al (2000) analysed by the TRAP method and found hTERT expression in 89% of glioblastoma samples.…”

“…In the present study, four out of 18 meningiomas and three out of eight grade I meningiomas were positive for hTERT mRNA expression (data not shown), suggesting also a trend for increased expression with histologic grading of meningiomas. On the other hand, studies by Falchetti et al (1999), Harada et al (2000), Cabuy and de Ridder (2001) and Tchirkov et al (2003) have generated conflicting results regarding the prognostic utility of telomerase expression in meningiomas and gliomas (predominantly of high grade).…”

Amplification of telomerase (hTERT) gene is a poor prognostic marker in non-small-cell lung cancer

“…Activations of the hTERT or ALT pathways are obligate for senescence bypass and for neoplastic transformation of normal cells (Newbold, 2002). Telomerase activity and/or hTERT expression are increased in cancers and are prognostic factors in various cancer types (Harada et al, 1999;Bieche et al, 2000;Lee et al, 2001;Marchetti et al, 2002;Wang et al, 2002;Fujita et al, 2003;Krams et al, 2003;Ohali et al, 2003;Tchirkov et al, 2003;Lantuejoul et al, 2004). However, the clinical impact of hTERT expression or activity in non-small-cell lung cancer (NSCLC) remains controversial (Albanell et al, 1997;Taga et al, 1999;Hirashima et al, 2000;Komiya et al, 2000;Toomey et al, 2001;Marchetti et al, 2002;Wang et al, 2002;Fujita et al, 2003;Wu et al, 2003;Hsu et al, 2004;Lantuejoul et al, 2004).…”

RNA interference mediated downregulation of human telomerase reverse transcriptase (hTERT) in LN18 cells

“…This makes hTERT as an excellent candidate gene to target in anticancer therapy (Shay et al 2001;Cong et al 2002). It has been reported that, more than 50 % of gliomas have increased telomerase activity (Langford et al 1995;Nakatani et al 1997;Le et al 1998;Sugita et al 2000;Tchirkov et al 2003). Several studies showed that, silencing of hTERT resulted in progressive shortening of telomeres and thereby inhibiting cellular proliferation and induce apoptosis in various cancer cells (Natarajan et al 2004;Zhao et al 2005;Wang et al 2007;Shi et al 2014).…”

“…Almost 80-90 % of human cancers display telomerase activity. Several studies showed that more than 50 % of gliomas display telomerase activity and its detection rates increases with the grades of malignancy (Langford et al 1995;Nakatani et al 1997;Sano et al 1998;Tchirkov et al 2003). Much attention has been given to telomerase, however, telomerase independent mechanism like alternative lengthening of telomeres (ALT) can also maintain telomere lengths in cancer cells by homologous recombination between telomere sister chromatids (Cesare and Reddel 2010).…”