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. 2003 Feb 24;88(4):516-20.
doi: 10.1038/sj.bjc.6600754.

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

A Tchirkov  1 , C Rolhion, J-L Kémény, B Irthum, S Puget, T Khalil, O Chinot, F Kwiatkowski, B Périssel, P Vago, P Verrelle
Affiliations

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

A Tchirkov et al. Br J Cancer. .

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 (< pr = 25%) and high (>25%), we found that the overall survival among hTERT-positive GBMs was significantly worse in high hTERT expressors than in low hTERT expressors (P=0.0082). We conclude that the amount of hTERT mRNA may represent a diagnostic and prognostic indicator for GBM patients.

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Figures

Figure 1
Figure 1
Example of real-time PCR quantification of hTERT in tumour samples. Amplification profiles obtained on the LightCycler are presented for hTERT (upper graph) and ABL (lower graph) transcripts. Linear regressions of standard dilution series, indicating accuracy of the analysis, are shown on the upper left part of each graph. Calculation of the number of hTERT and ABL transcripts was done by using these standard curves. One of the standards was included in each PCR run (amplification profiles shown as solid lines, 105 molecules). For each sample, the number of hTERT transcripts was divided by the number of ABL transcripts in order to standardise the level of hTERT mRNA. The obtained ratios expressed as percentage are shown.
Figure 2
Figure 2
Individual hTERT/ABL ratios (%) determined in glioma samples according to the investigated tumour types. The mean values are shown as horizontal bars for each group: low-grade tumours (0.2%), anaplastic gliomas (3.7%), GBMs (37.8%).
Figure 3
Figure 3
Survival of GBM patients in relation to hTERT status in their tumours. Patients, whose tumours expressed hTERT at low levels, survived significantly longer (19 months, median) than those patients who showed high hTERT levels in their tumours (8 months, median) or than hTERT-negative patients (8 months, median) did. Note the very similar survival period for high hTERT expressors and hTERT-negative patients.
See this image and copyright information in PMC

References

    1. Bamber D (1975) The area above the ordinal dominance graph and the area below the receiver operating characteristic graph. J Math Psychol 12: 387–395
    1. Bryan TM, Reddel RR (1997) Telomere dynamics and telomerase activity in in vitro immortalised human cells. Eur J Cancer 33: 767–773 - PubMed
    1. Buonamici S, Ottaviani E, Testoni N, Montefusco V, Visani G, Bonifazi F, Amabile M, Terragna C, Ruggeri D, Piccaluga PP, Isidori A, Malagola M, Baccarani M, Tura S, Martinelli G (2002) Real-time quantitation of minimal residual disease in inv(16)-positive acute myeloid leukemia may indicate risk for clinical relapse and may identify patients in a curable state. Blood 99: 443–449 - PubMed
    1. Chakravarti A, Delaney MA, Noll E, Black PM, Loeffler JS, Muzikansky A, Dyson NJ (2001) Prognostic and pathologic significance of quantitative protein expression profiling in human gliomas. Clin Cancer Res 7: 2387–2395 - PubMed
    1. Counter CM, Hirte HW, Bacchetti S, Harley CB (1994) Telomerase activity in human ovarian carcinoma. Proc Natl Acad Sci USA 9: 2900–2904 - PMC - PubMed