TY - JOUR
T1 - Telomere maintenance mechanisms in malignant peripheral nerve sheath tumors
T2 - Expression and prognostic relevance
AU - Venturini, Lorenza
AU - Daidone, Maria Grazia
AU - Motta, Rosita
AU - Cimino-Reale, Graziella
AU - Hoare, Stacey F.
AU - Gronchi, Alessandro
AU - Folini, Marco
AU - Keith, William Nicol
AU - Zaffaroni, Nadia
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - alternative lengthening of telomeres
KW - malignant peripheral nerve sheath tumors
KW - s hwannoma
KW - telomerase
KW - telomere maintenance mechanisms
UR - http://www.scopus.com/inward/record.url?scp=84862232995&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862232995&partnerID=8YFLogxK
U2 - 10.1093/neuonc/nos083
DO - 10.1093/neuonc/nos083
M3 - Article
C2 - 22516689
AN - SCOPUS:84862232995
VL - 14
SP - 736
EP - 744
JO - Neuro-Oncology
JF - Neuro-Oncology
SN - 1522-8517
IS - 6
ER -