Telomerase in intracranial meningiomas

Abstract

Telomere length maintenance is essential for tumorigenesis; most human tumors stabilize their chromosome ends via the activity of a specialized reverse transcriptase, telomerase, that uses the template region of the RNA moiety complementary to the TTAGGG repeat to synthesize one strand of telomeric DNA. Meningiomas are estimated to constitute between 13% and 26% of primary intracranial tumors. The aim of this study was to evaluate telomerase activity and its messenger expression in meningiomas in relation to their different histologic pattern and grade of cytonuclear atypies, which are associated with relapse, and consequently represent the most important parameter for the evaluation of the clinical behavior of this tumor. Telomerase activity was examined by the telomeric repeat amplification protocol (TRAP) assay in 32 meningiomas (26 typical and 6 atypical/anaplastic). Telomerase messenger expression (hTERT mRNA) was evaluated by reverse transcription-PCR analysis in the same group of tumors. Telomerase activity ranged from undetectable to low levels in 19/26 (73%) of typical meningiomas, while all the atypical/anaplastic meningiomas showed medium-high levels of activity (>3 TPG units, median value), (chi(2) test; p=0.001). The levels of telomerase in terms of its messenger level expression overlapped the activity; a significant association between telomerase activity and hTERT mRNA expression was also found (chi(2) test; p=0.01). Moreover, 2 atypical/anaplastic meningiomas of our series relapsed; in these samples we found high levels of telomerase, both in terms of activity and mRNA expression. Telomerase activity and its hTERT mRNA expression tended to increase as the histologic grading of intracranial tumors increased, suggesting a role of telomerase reactivation in the progression of these tumors. Moreover, our results indicate RT-PCR assay as a rapid tool to identify and quantify telomerase RNA in intracranial meningiomas as in other human tumor models.