Telomerase activity (TA) and the expression of its enzymatic subunits, which have been demonstrated in many tumors, remain poorly investigated in tumors associated with neurofibromatosis type 1 (NF1). In this study, we analysed the association of TA and the expression of telomerase RNA (TR) and telomerase reverse transcriptase (TERT) in 23 malignant peripheral nerve sheath tumors (MPNST) (17 high grade and 6 low grade tumors), 11 plexiform neurofibromas (PNF) and 6 dermal neurofibro- mas (DNF). TA was studied using telomerase repeat amplification protocol (TRAP) assay and expression of TR and TERT was investigated using reverse transcription PCR (RT-PCR) and real-time PCR. TA was detected in 14 out of 17 (82%) high grade MPNST, whereas all 6 low grade MPNSTand 17 benign tumors were telomerase negative. The TERT transcripts were detected in all high grade MPNST, 50% of the low grade MPNST, and 4 benign tumors. However, the expression level of the TERT strik- ingly correlated with TA and high grade MPNST. Thus, while TERTexpression was similar in both low grade MPNSTand PNF (P 5 0.115), it was significantly higher in high grade MPNSTwhen compared to either low grade MPNST (P 5 0.042), PNF (P 5 0.001) or DNF tumors (P 5 0.010). These findings indicate that TA and expression level of TERTare potential markers for high grade malignancy in NF1 patients. This article contains Supplementary Material available at http://www.interscience.wiley.com/ jpages/1045-2257/suppmat.
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