Expression of Telomerase RNA, Telomerase Activity, and Telomere Length in Human Gliomas

Morii, Ken; Tanaka, Ryuichi; Onda, Kiyoshi; Tsumanuma, Itaru; Yoshimura, Jyunichi

doi:10.1006/bbrc.1997.7562

Cited by 29 publications

(23 citation statements)

References 24 publications

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“…Telomerase-negative GBMs might achieve immortalisation by an alternative mechanism of telomere length stabilisation. Evidence in support of this hypothesis has been reported in a study of telomere length in gliomas (Morii et al, 1997). Compared with telomerase-positive gliomas, telomerasenegative gliomas were found to have very long and heterogeneous telomeres, characteristics seen in tumour cells that have acquired an alternative mechanism for lengthening their telomeres.…”

Section: Discussionmentioning

confidence: 69%

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

Tchirkov

Rolhion

Jl³

et al. 2003

Br J Cancer

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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.

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Section: Discussionmentioning

confidence: 69%

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

Tchirkov

Rolhion

Jl³

et al. 2003

Br J Cancer

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“…The author concluded that short telomeres are linked to a further state of progression and a more aggressive behaviour for these tumours. Also other studies on telomere length for intracranial tumours found a shortening of the telomeres for telomerase positive tumours (14,35). In our study, most tumours (96%) had shorter telomeres compared to normal intracranial tissue.…”

Section: Discussionmentioning

confidence: 87%

“…As telomeres are essential for DNA replication and control of cell division (1), the regulation of their length has been a focus of research on tumourigenesis (13,14). It has been demonstrated that telomere shortening, which occurs at every successive cell division in somatic cells, is stopped in most tumours, which leads to immortalisation through the activation of telomerase.…”

Section: Discussionmentioning

confidence: 99%

“…If tumour cells turn on telomerase, the expression of this enzyme may lead to unlimited proliferation and immortality for tumour cells (11). Some results have already been published on telomerase and telomeres in intracranial tumours (12)(13)(14), showing a correlation between telomerase activity and histopathological grading. It has been reported that hTERT rather than telomerase activity could be used as a prognostic marker for progression and potential recurrence (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

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Relation between telomerase activity, hTERT and telomere length for intracranial tumours

Maes¹,

Neste²,

Damme³

et al. 2007

Oncol Rep

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Abstract. Human linear chromosomes are capped by specialized DNA-protein structures called telomeres. The present study analysed the telomerase activity, hTERT protein and telomere length in meningiomas and gliomas in relation to their WHO grading. Fifty-three freshly dissected tumour biopsies were analysed for telomerase activity, hTERT protein expression and telomere length. Telomerase activity was examined in 41 of the 53 biopsies. Telomerase activity was detected in 3 of 35 (8.6%) screened meningiomas (1 benign, 1 atypical and 1 malignant meningioma). For hTERT expression, 56.4% of meningiomas were positive with a mean labelling index (hTERT LI) of 31.3% (SD=26.5) for the hTERT positive meningiomas. The mean telomere length for meningiomas was 6.983 kb (SD=1.969). For gliomas, no active telomerase was detected in 2 low-grade astrocytomas, whereas three of the four screened glioblastomas were positive for telomerase activity. The only hTERT protein positive astrocytoma had a mean labelling index of 9.0%. On the other hand, the hTERT LI for glioblastomas was 53.6% (SD=28.0). The two low-grade astrocytomas had a telomere length of 14.310 and 9.236 kb. The anaplastic astrocytoma had a telomere length of 4.903 kb and the glioblastomas 5.767 kb (SD=2.042). The normal meningeal and neuronal tissue is negative for telomerase activity and hTERT. The length was ±10.000 kb. These results indicate that telomere shortening may be a critical step in pathogenesis of atypical and malignant meningiomas and gliomas. Critical telomere shortening in vitro was shown to activate telomerase.

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“…This neoplasm is highly proliferative and conventional multimodal therapy does not change its poor prognosis (Burger and Green, 1987;Davis et al, 1998;Leenstra et al, 1998;Galanis et al, 1998). In human gliomas, activation of telomerase is frequently associated with malignant tumor progression (Langford et al, 1995;Morii et al, 1999;DeMasters et al;Sallinen et al, 1997;Nakatani et al, 1997;Kleinschmidt-DeMasters et al, 1998;Le et al, 1998;Chong et al, 1998;Hiraga et al, 1998;Falchetti et al,1999b;Huang et al, 1999). It has been suggested that telomerase activity in GBM tumors may be related to tumorigenesis as secondary GBM tumors, which progress from low-grade gliomas, constantly exhibit telomerase activity, whereas telomerase activity can be detected only in 63% of primary de novo GBM tumors (Hiraga et al, 1998).…”

mentioning

confidence: 99%

In situ detection of telomerase catalytic subunit mRNA in glioblastoma multiforme

et al. 2000

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Expression of Telomerase RNA, Telomerase Activity, and Telomere Length in Human Gliomas

Cited by 29 publications

References 24 publications

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

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

Relation between telomerase activity, hTERT and telomere length for intracranial tumours

In situ detection of telomerase catalytic subunit mRNA in glioblastoma multiforme

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