Telomerase activity in 144 brain tumours

Abstract

Summary Unlimited proliferation in immortalized cells is believed to be highly dependent on the activity of telomerase, a ribonucleoprotein that synthesizes telomeric repeats onto chromosome ends. Using a polymerase chain reaction-based telomeric repeat amplification protocol (TRAP) assay, we analysed telomerase activity in 99 benign and 45 malignant brain tumours. The TRAP assay results were quantitated by normalizing the telomerase activity of each specimen to that of human glioma cell line T98G to obtain the relative telomerase activity. Telomerase activity was also assessed visually from the autoradiograms as being positive or negative. One hundred and sixteen tumours with negative telomerase activity had null relative telomerase activity, whereas 28 tumours with positive telomerase activity had relative telomerase activities of 12-84.3% (mean 0% vs 36.1 ± 19.3%, P < 0.0001). Thus, quantification of telomerase activity confirmed the results of the visual evaluation of telomerase activity on autoradiograms. Based on the assessment, malignant brain tumours had a higher positive rate of telomerase activity than benign tumours (57.8% vs 2.0%, P < 0.001). These data indicate that positive telomerase activity is strongly associated with malignant brain tumours and is rather rare in benign tumours, such as neurinomas or meningiomas.

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

“…Furthermore, the percentage of TERT promoter mutations in oligoastrocytomas, gliomas with a mixed origin, is intermediate between that of oligodendrogliomas and astrocytomas [58]. These findings fit with the reported data on telomerase activity in gliomas which is considerably higher in GBM (50-89 %) and oligodendrogliomas (75-100 %), than in astrocytomas (0-45 %) [49,67,106]. The low frequency of TERT promoter mutations and telomerase activity in grades II and III astrocytomas can be explained by the high prevalence of ATRX mutations, one of the most frequent mutations in this type of glioma [56].…”

Telomerase as a therapeutic target for malignant gliomas

“…Telomerase activity, which is generally undetectable in normal somatic cells, is expressed in approximately 90% of tumors (Kim et al, 1994;Broccoli et al, 1995;Hiyama et al, 1995). In malignant gliomas, telomerase activity is very often detected (Table 1) (Langford et al, 1995;DeMasters et al, 1997;Sallinen et al, 1997;Sano et al, 1998;Kleinschmidt-DeMasters et al, 1998;Chong et al, 1998;Hiraga et al, 1998;Le et al, 1998;Weil et al, 1999;Carroll et al, 1999;Falchetti et al, 1999;Huang et al, 1999;Kleinschmidt-DeMasters et al, 2000;Harada et al, 2000). In Grade I or II of gliomas, telomerase activity is detected in 0% or 0 to 33%, respectively.…”

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

“…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).…”