Telomere maintenance mechanisms in malignant peripheral nerve sheath tumors: Expression and prognostic relevance

Lorenza Venturini, Maria Grazia Daidone, Rosita Motta, Graziella Cimino-Reale, Stacey F. Hoare, Alessandro Gronchi, Marco Folini, William Nicol Keith, Nadia Zaffaroni

Research output: Contribution to journalArticlepeer-review


This study investigated the prevalence and the prognostic relevance of the 2 known telomere maintenance mechanisms (TMMs), telomerase activity (TA) and alternative lengthening of telomeres (ALT), in malignant peripheral nerve sheath tumors (MPNST). In 57 specimens from 49 patients with MPNST (35 sporadic, 14 neurofibromatosis type 1-related), TA was determined using the telomeric repeat amplification protocol, and ALT was detected by assaying ALT-associated promyelocytic leukemia bodies (APB) and terminal restriction fragment (TRF) length distribution. TA or ALT (defined on the basis of APB) alone was found in 24.6 or 26.3 of the lesions, respectively, whereas 6 cases (10.5) were TA/ALT. A concordance between APB and TRF results in defining the ALT status was observed in 44 of 57 cases (77.2; P = .0001). TA was more frequently expressed in samples from patients with neurofibromatosis type 1 than in those with sporadic disease (60 vs 29.4, P 0.087). In the overall series, TA proved to be prognostic for 5-year disease-specific death (hazard ratio, 3.78; 95 confidence interval [CI], 1.608.95; P = .002), even when adjusted for the presence of neurofibromatosis type 1 (hazard ratio, 4.22; 95 CI, 1.8049.874; P = .001) and margin status after surgery (hazard ratio, 5.78; 95 CI, 2.1915.26; P = .001). Conversely, ALT did not significantly affect clinical outcome of MPNST using either APB expression (hazard ratio, 1.25; 95 CI 0.542.89; P 0.605) or TRF distribution (hazard ratio, 0.57; 95 CI, 0.171.96; P .375) as the detection approach. Our results indicate for the first time that both TMMs, TA and ALT, are present in MPNST and differentially affect patient prognosis.

Original languageEnglish
Pages (from-to)736-744
Number of pages9
Issue number6
Publication statusPublished - Jun 2012


  • alternative lengthening of telomeres
  • malignant peripheral nerve sheath tumors
  • s hwannoma
  • telomerase
  • telomere maintenance mechanisms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology


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