title: Telomerase activity is a biomarker for high grade malignant peripheral nerve sheath tumors in neurofibromatosis type 1 individuals.
abstract: 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 neurofibromas (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 MPNST and 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 strikingly correlated with TA and high grade MPNST. Thus, while TERT expression was similar in both low grade MPNST and PNF (P = 0.115), it was significantly higher in high grade MPNST when compared to either low grade MPNST (P = 0.042), PNF (P = 0.001) or DNF tumors (P = 0.010). These findings indicate that TA and expression level of TERT are potential markers for high grade malignancy in NF1 patients.
authors: Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff, UK. mantripragadakk@cardiff.ac.uk
authors: Kiran K
authors: KK
authors: Mantripragada
authors: Matthew
authors: M
authors: Caley
authors: Phil
authors: P
authors: Stephens
authors: Christopher J
authors: CJ
authors: Jones
authors: Lan
authors: L
authors: Kluwe
authors: Abhijit
authors: A
authors: Guha
authors: Victor
authors: V
authors: Mautner
authors: Meena
authors: M
authors: Upadhyaya
mesh_terms: D015415:Biomarkers / Q000032:analysis; D006801:Humans; D018317:Nerve Sheath Neoplasms / Q000175:diagnosis* / Q000209:etiology; D009455:Neurofibroma / Q000175:diagnosis; D018318:Neurofibroma, Plexiform / Q000175:diagnosis; D009456:Neurofibromatosis 1 / Q000150:complications*; D012313:RNA / Q000032:analysis*; D012720:Severity of Illness Index; D019098:Telomerase / Q000032:analysis* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase