Skip to main content
Top
Published in: Journal of Neuro-Oncology 1/2014

01-03-2014 | Laboratory Investigation

Prognostic significance of telomere maintenance mechanisms in pediatric high-grade gliomas

Authors: Kathleen Dorris, Matthew Sobo, Arzu Onar-Thomas, Eshini Panditharatna, Charles B. Stevenson, Sharon L. Gardner, Mariko D. DeWire, Christopher R. Pierson, Randal Olshefski, Sandra A. Rempel, Stewart Goldman, Lili Miles, Maryam Fouladi, Rachid Drissi

Published in: Journal of Neuro-Oncology | Issue 1/2014

Login to get access

Abstract

Children with high-grade glioma, including diffuse intrinsic pontine glioma (DIPG), have a poor prognosis despite multimodal therapy. Identifying novel therapeutic targets is critical to improve their outcome. We evaluated prognostic roles of telomere maintenance mechanisms in children with HGG, including DIPG. A multi-institutional retrospective study was conducted involving 50 flash-frozen HGG (35 non-brainstem; 15 DIPG) tumors from 45 children (30 non-brainstem; 15 DIPG). Telomerase activity, expression of hTERT mRNA (encoding telomerase catalytic component) and TERC (telomerase RNA template) and alternative lengthening of telomeres (ALT) mechanism were assayed. Cox Proportional Hazard regression analyses assessed association of clinical and pathological variables, TERC and hTERT levels, telomerase activity, and ALT use with progression-free or overall survival (OS). High TERC and hTERT expression was detected in 13/28 non-brainstem HGG samples as compared to non-neoplastic controls. High TERC and hTERT expression was identified in 13/15 and 11/15 DIPG samples, respectively, compared to controls. Evidence of ALT was noted in 3/11 DIPG and 10/19 non-brainstem HGG specimens. ALT and telomerase use were identified in 4/19 non-brainstem HGG and 2/11 DIPG specimens. In multivariable analyses, increased TERC and hTERT levels were associated with worse OS in patients with non-brainstem HGG, after controlling for tumor grade or resection extent. Children with HGG and DIPG, have increased hTERT and TERC expression. In children with non-brainstem HGG, increased TERC and hTERT expression levels are associated with a worse OS, making telomerase a promising potential therapeutic target in pediatric HGG.
Appendix
Available only for authorised users
Literature
2.
go back to reference Feng J, Funk WD, Wang SS, Weinrich SL, Avilion AA, Chiu CP, Adams RR, Chang E, Allsopp RC, Yu J et al (1995) The RNA component of human telomerase. Science 269(5228):1236–1241PubMedCrossRef Feng J, Funk WD, Wang SS, Weinrich SL, Avilion AA, Chiu CP, Adams RR, Chang E, Allsopp RC, Yu J et al (1995) The RNA component of human telomerase. Science 269(5228):1236–1241PubMedCrossRef
3.
go back to reference Weinrich SL, Pruzan R, Ma L, Ouellette M, Tesmer VM, Holt SE, Bodnar AG, Lichtsteiner S, Kim NW, Trager JB, Taylor RD, Carlos R, Andrews WH, Wright WE, Shay JW, Harley CB, Morin GB (1997) Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT. Nat Genet 17(4):498–502. doi:10.1038/ng1297-498 PubMedCrossRef Weinrich SL, Pruzan R, Ma L, Ouellette M, Tesmer VM, Holt SE, Bodnar AG, Lichtsteiner S, Kim NW, Trager JB, Taylor RD, Carlos R, Andrews WH, Wright WE, Shay JW, Harley CB, Morin GB (1997) Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT. Nat Genet 17(4):498–502. doi:10.​1038/​ng1297-498 PubMedCrossRef
4.
go back to reference Counter CM, Avilion AA, LeFeuvre CE, Stewart NG, Greider CW, Harley CB, Bacchetti S (1992) Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J 11(5):1921–1929PubMedCentralPubMed Counter CM, Avilion AA, LeFeuvre CE, Stewart NG, Greider CW, Harley CB, Bacchetti S (1992) Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J 11(5):1921–1929PubMedCentralPubMed
5.
go back to reference Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266(5193):2011–2015PubMedCrossRef Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266(5193):2011–2015PubMedCrossRef
6.
8.
go back to reference Takakura M, Kyo S, Kanaya T, Tanaka M, Inoue M (1998) Expression of human telomerase subunits and correlation with telomerase activity in cervical cancer. Cancer Res 58(7):1558–1561PubMed Takakura M, Kyo S, Kanaya T, Tanaka M, Inoue M (1998) Expression of human telomerase subunits and correlation with telomerase activity in cervical cancer. Cancer Res 58(7):1558–1561PubMed
9.
go back to reference Wu A, Ichihashi M, Ueda M (1999) Correlation of the expression of human telomerase subunits with telomerase activity in normal skin and skin tumors. Cancer 86(10):2038–2044PubMedCrossRef Wu A, Ichihashi M, Ueda M (1999) Correlation of the expression of human telomerase subunits with telomerase activity in normal skin and skin tumors. Cancer 86(10):2038–2044PubMedCrossRef
10.
go back to reference Poole JC, Andrews LG, Tollefsbol TO (2001) Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT). Gene 269(1–2):1–12PubMedCrossRef Poole JC, Andrews LG, Tollefsbol TO (2001) Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT). Gene 269(1–2):1–12PubMedCrossRef
11.
go back to reference Avilion AA, Piatyszek MA, Gupta J, Shay JW, Bacchetti S, Greider CW (1996) Human telomerase RNA and telomerase activity in immortal cell lines and tumor tissues. Cancer Res 56(3):645–650PubMed Avilion AA, Piatyszek MA, Gupta J, Shay JW, Bacchetti S, Greider CW (1996) Human telomerase RNA and telomerase activity in immortal cell lines and tumor tissues. Cancer Res 56(3):645–650PubMed
12.
13.
go back to reference Langford LA, Piatyszek MA, Xu R, Schold SC Jr, Shay JW (1995) Telomerase activity in human brain tumours. Lancet 346(8985):1267–1268PubMedCrossRef Langford LA, Piatyszek MA, Xu R, Schold SC Jr, Shay JW (1995) Telomerase activity in human brain tumours. Lancet 346(8985):1267–1268PubMedCrossRef
14.
go back to reference Chong EY, Lam PY, Poon WS, Ng HK (1998) Telomerase expression in gliomas including the nonastrocytic tumors. Hum Pathol 29(6):599–603PubMedCrossRef Chong EY, Lam PY, Poon WS, Ng HK (1998) Telomerase expression in gliomas including the nonastrocytic tumors. Hum Pathol 29(6):599–603PubMedCrossRef
15.
go back to reference Le S, Zhu JJ, Anthony DC, Greider CW, Black PM (1998) Telomerase activity in human gliomas. Neurosurgery 42(5):1120–1124 (discussion 1124–1125PubMedCrossRef Le S, Zhu JJ, Anthony DC, Greider CW, Black PM (1998) Telomerase activity in human gliomas. Neurosurgery 42(5):1120–1124 (discussion 1124–1125PubMedCrossRef
16.
go back to reference Huang F, Kanno H, Yamamoto I, Lin Y, Kubota Y (1999) Correlation of clinical features and telomerase activity in human gliomas. J Neurooncol 43(2):137–142PubMedCrossRef Huang F, Kanno H, Yamamoto I, Lin Y, Kubota Y (1999) Correlation of clinical features and telomerase activity in human gliomas. J Neurooncol 43(2):137–142PubMedCrossRef
17.
go back to reference Boldrini L, Pistolesi S, Gisfredi S, Ursino S, Ali G, Pieracci N, Basolo F, Parenti G, Fontanini G (2006) Telomerase activity and hTERT mRNA expression in glial tumors. Int J Oncol 28(6):1555–1560PubMed Boldrini L, Pistolesi S, Gisfredi S, Ursino S, Ali G, Pieracci N, Basolo F, Parenti G, Fontanini G (2006) Telomerase activity and hTERT mRNA expression in glial tumors. Int J Oncol 28(6):1555–1560PubMed
18.
go back to reference Bryan TM, Marusic L, Bacchetti S, Namba M, Reddel RR (1997) The telomere lengthening mechanism in telomerase-negative immortal human cells does not involve the telomerase RNA subunit. Hum Mol Genet 6(6):921–926PubMedCrossRef Bryan TM, Marusic L, Bacchetti S, Namba M, Reddel RR (1997) The telomere lengthening mechanism in telomerase-negative immortal human cells does not involve the telomerase RNA subunit. Hum Mol Genet 6(6):921–926PubMedCrossRef
20.
go back to reference Heaphy CM, Subhawong AP, Hong SM, Goggins MG, Montgomery EA, Gabrielson E, Netto GJ, Epstein JI, Lotan TL, Westra WH, Shih Ie M, Iacobuzio-Donahue CA, Maitra A, Li QK, Eberhart CG, Taube JM, Rakheja D, Kurman RJ, Wu TC, Roden RB, Argani P, De Marzo AM, Terracciano L, Torbenson M, Meeker AK (2011) Prevalence of the alternative lengthening of telomeres telomere maintenance mechanism in human cancer subtypes. Am J Pathol 179(4):1608–1615. doi:10.1016/j.ajpath.2011.06.018 PubMedCentralPubMedCrossRef Heaphy CM, Subhawong AP, Hong SM, Goggins MG, Montgomery EA, Gabrielson E, Netto GJ, Epstein JI, Lotan TL, Westra WH, Shih Ie M, Iacobuzio-Donahue CA, Maitra A, Li QK, Eberhart CG, Taube JM, Rakheja D, Kurman RJ, Wu TC, Roden RB, Argani P, De Marzo AM, Terracciano L, Torbenson M, Meeker AK (2011) Prevalence of the alternative lengthening of telomeres telomere maintenance mechanism in human cancer subtypes. Am J Pathol 179(4):1608–1615. doi:10.​1016/​j.​ajpath.​2011.​06.​018 PubMedCentralPubMedCrossRef
21.
go back to reference McDonald KL, McDonnell J, Muntoni A, Henson JD, Hegi ME, von Deimling A, Wheeler HR, Cook RJ, Biggs MT, Little NS, Robinson BG, Reddel RR, Royds JA (2010) Presence of alternative lengthening of telomeres mechanism in patients with glioblastoma identifies a less aggressive tumor type with longer survival. J Neuropathol Exp Neurol 69(7):729–736. doi:10.1097/NEN.0b013e3181e576cf PubMedCrossRef McDonald KL, McDonnell J, Muntoni A, Henson JD, Hegi ME, von Deimling A, Wheeler HR, Cook RJ, Biggs MT, Little NS, Robinson BG, Reddel RR, Royds JA (2010) Presence of alternative lengthening of telomeres mechanism in patients with glioblastoma identifies a less aggressive tumor type with longer survival. J Neuropathol Exp Neurol 69(7):729–736. doi:10.​1097/​NEN.​0b013e3181e576cf​ PubMedCrossRef
22.
go back to reference Hakin-Smith V, Jellinek DA, Levy D, Carroll T, Teo M, Timperley WR, McKay MJ, Reddel RR, Royds JA (2003) Alternative lengthening of telomeres and survival in patients with glioblastoma multiforme. Lancet 361(9360):836–838PubMedCrossRef Hakin-Smith V, Jellinek DA, Levy D, Carroll T, Teo M, Timperley WR, McKay MJ, Reddel RR, Royds JA (2003) Alternative lengthening of telomeres and survival in patients with glioblastoma multiforme. Lancet 361(9360):836–838PubMedCrossRef
23.
go back to reference Goldberg AD, Banaszynski LA, Noh KM, Lewis PW, Elsaesser SJ, Stadler S, Dewell S, Law M, Guo X, Li X, Wen D, Chapgier A, DeKelver RC, Miller JC, Lee YL, Boydston EA, Holmes MC, Gregory PD, Greally JM, Rafii S, Yang C, Scambler PJ, Garrick D, Gibbons RJ, Higgs DR, Cristea IM, Urnov FD, Zheng D, Allis CD (2010) Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell 140(5):678–691. doi:10.1016/j.cell.2010.01.003 PubMedCentralPubMedCrossRef Goldberg AD, Banaszynski LA, Noh KM, Lewis PW, Elsaesser SJ, Stadler S, Dewell S, Law M, Guo X, Li X, Wen D, Chapgier A, DeKelver RC, Miller JC, Lee YL, Boydston EA, Holmes MC, Gregory PD, Greally JM, Rafii S, Yang C, Scambler PJ, Garrick D, Gibbons RJ, Higgs DR, Cristea IM, Urnov FD, Zheng D, Allis CD (2010) Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell 140(5):678–691. doi:10.​1016/​j.​cell.​2010.​01.​003 PubMedCentralPubMedCrossRef
26.
go back to reference Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K, Sturm D, Fontebasso AM, Quang DA, Tonjes M, Hovestadt V, Albrecht S, Kool M, Nantel A, Konermann C, Lindroth A, Jager N, Rausch T, Ryzhova M, Korbel JO, Hielscher T, Hauser P, Garami M, Klekner A, Bognar L, Ebinger M, Schuhmann MU, Scheurlen W, Pekrun A, Fruhwald MC, Roggendorf W, Kramm C, Durken M, Atkinson J, Lepage P, Montpetit A, Zakrzewska M, Zakrzewski K, Liberski PP, Dong Z, Siegel P, Kulozik AE, Zapatka M, Guha A, Malkin D, Felsberg J, Reifenberger G, von Deimling A, Ichimura K, Collins VP, Witt H, Milde T, Witt O, Zhang C, Castelo-Branco P, Lichter P, Faury D, Tabori U, Plass C, Majewski J, Pfister SM, Jabado N (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482(7384):226–231. doi:10.1038/nature10833 PubMedCrossRef Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K, Sturm D, Fontebasso AM, Quang DA, Tonjes M, Hovestadt V, Albrecht S, Kool M, Nantel A, Konermann C, Lindroth A, Jager N, Rausch T, Ryzhova M, Korbel JO, Hielscher T, Hauser P, Garami M, Klekner A, Bognar L, Ebinger M, Schuhmann MU, Scheurlen W, Pekrun A, Fruhwald MC, Roggendorf W, Kramm C, Durken M, Atkinson J, Lepage P, Montpetit A, Zakrzewska M, Zakrzewski K, Liberski PP, Dong Z, Siegel P, Kulozik AE, Zapatka M, Guha A, Malkin D, Felsberg J, Reifenberger G, von Deimling A, Ichimura K, Collins VP, Witt H, Milde T, Witt O, Zhang C, Castelo-Branco P, Lichter P, Faury D, Tabori U, Plass C, Majewski J, Pfister SM, Jabado N (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482(7384):226–231. doi:10.​1038/​nature10833 PubMedCrossRef
27.
go back to reference Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J, Qu C, Ding L, Huether R, Parker M, Zhang J, Gajjar A, Dyer MA, Mullighan CG, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Ellison DW, Baker SJ (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44(3):251–253. doi:10.1038/ng.1102 PubMedCentralPubMedCrossRef Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J, Qu C, Ding L, Huether R, Parker M, Zhang J, Gajjar A, Dyer MA, Mullighan CG, Gilbertson RJ, Mardis ER, Wilson RK, Downing JR, Ellison DW, Baker SJ (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44(3):251–253. doi:10.​1038/​ng.​1102 PubMedCentralPubMedCrossRef
28.
go back to reference Khuong-Quang DA, Buczkowicz P, Rakopoulos P, Liu XY, Fontebasso AM, Bouffet E, Bartels U, Albrecht S, Schwartzentruber J, Letourneau L, Bourgey M, Bourque G, Montpetit A, Bourret G, Lepage P, Fleming A, Lichter P, Kool M, von Deimling A, Sturm D, Korshunov A, Faury D, Jones DT, Majewski J, Pfister SM, Jabado N, Hawkins C (2012) K27 M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol 124(3):439–447. doi:10.1007/s00401-012-0998-0 PubMedCentralPubMedCrossRef Khuong-Quang DA, Buczkowicz P, Rakopoulos P, Liu XY, Fontebasso AM, Bouffet E, Bartels U, Albrecht S, Schwartzentruber J, Letourneau L, Bourgey M, Bourque G, Montpetit A, Bourret G, Lepage P, Fleming A, Lichter P, Kool M, von Deimling A, Sturm D, Korshunov A, Faury D, Jones DT, Majewski J, Pfister SM, Jabado N, Hawkins C (2012) K27 M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol 124(3):439–447. doi:10.​1007/​s00401-012-0998-0 PubMedCentralPubMedCrossRef
29.
go back to reference Takakura M, Kyo S, Kanaya T, Hirano H, Takeda J, Yutsudo M, Inoue M (1999) Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells. Cancer Res 59(3):551–557PubMed Takakura M, Kyo S, Kanaya T, Hirano H, Takeda J, Yutsudo M, Inoue M (1999) Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells. Cancer Res 59(3):551–557PubMed
30.
go back to reference Kimura M, Stone RC, Hunt SC, Skurnick J, Lu X, Cao X, Harley CB, Aviv A (2010) Measurement of telomere length by the Southern blot analysis of terminal restriction fragment lengths. Nat Protoc 5(9):1596–1607. doi:10.1038/nprot.2010.124 PubMedCrossRef Kimura M, Stone RC, Hunt SC, Skurnick J, Lu X, Cao X, Harley CB, Aviv A (2010) Measurement of telomere length by the Southern blot analysis of terminal restriction fragment lengths. Nat Protoc 5(9):1596–1607. doi:10.​1038/​nprot.​2010.​124 PubMedCrossRef
31.
go back to reference Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3(6):1101–1108PubMedCrossRef Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3(6):1101–1108PubMedCrossRef
32.
go back to reference Holt SENJ, Wright WE, Shay JW (1996) Comparison of the telomeric repeat amplification protocol (TRAP) to the new TRAPeze Telomerase Detection Kit. Methods Cell Sci 18(3):237–248CrossRef Holt SENJ, Wright WE, Shay JW (1996) Comparison of the telomeric repeat amplification protocol (TRAP) to the new TRAPeze Telomerase Detection Kit. Methods Cell Sci 18(3):237–248CrossRef
33.
go back to reference Maitra A, Yashima K, Rathi A, Timmons CF, Rogers BB, Shay JW, Gazdar AF (1999) The RNA component of telomerase as a marker of biologic potential and clinical outcome in childhood neuroblastic tumors. Cancer 85(3):741–749PubMedCrossRef Maitra A, Yashima K, Rathi A, Timmons CF, Rogers BB, Shay JW, Gazdar AF (1999) The RNA component of telomerase as a marker of biologic potential and clinical outcome in childhood neuroblastic tumors. Cancer 85(3):741–749PubMedCrossRef
34.
go back to reference Dome JS, Bockhold CA, Li SM, Baker SD, Green DM, Perlman EJ, Hill DA, Breslow NE (2005) High telomerase RNA expression level is an adverse prognostic factor for favorable-histology Wilms’ tumor. J Clin Oncol 23(36):9138–9145. doi:10.1200/JCO.2005.00.562 PubMedCrossRef Dome JS, Bockhold CA, Li SM, Baker SD, Green DM, Perlman EJ, Hill DA, Breslow NE (2005) High telomerase RNA expression level is an adverse prognostic factor for favorable-histology Wilms’ tumor. J Clin Oncol 23(36):9138–9145. doi:10.​1200/​JCO.​2005.​00.​562 PubMedCrossRef
35.
go back to reference Choi LM, Kim NW, Zuo JJ, Gerbing R, Stram D, Lukens JN, Matthay KK, Seeger RC, Reynolds CP (2000) Telomerase activity by TRAP assay and telomerase RNA (hTR) expression are predictive of outcome in neuroblastoma. Med Pediatr Oncol 35(6):647–650PubMedCrossRef Choi LM, Kim NW, Zuo JJ, Gerbing R, Stram D, Lukens JN, Matthay KK, Seeger RC, Reynolds CP (2000) Telomerase activity by TRAP assay and telomerase RNA (hTR) expression are predictive of outcome in neuroblastoma. Med Pediatr Oncol 35(6):647–650PubMedCrossRef
36.
go back to reference Silvestre DC, Pineda JR, Hoffschir F, Studler JM, Mouthon MA, Pflumio F, Junier MP, Chneiweiss H, Boussin FD (2011) Alternative lengthening of telomeres in human glioma stem cells. Stem Cells 29(3):440–451. doi:10.1002/stem.600 PubMedCrossRef Silvestre DC, Pineda JR, Hoffschir F, Studler JM, Mouthon MA, Pflumio F, Junier MP, Chneiweiss H, Boussin FD (2011) Alternative lengthening of telomeres in human glioma stem cells. Stem Cells 29(3):440–451. doi:10.​1002/​stem.​600 PubMedCrossRef
37.
go back to reference Royds JA, Al Nadaf S, Wiles AK, Chen YJ, Ahn A, Shaw A, Bowie S, Lam F, Baguley BC, Braithwaite AW, MacFarlane MR, Hung NA, Slatter TL (2011) The CDKN2A G500 allele is more frequent in GBM patients with no defined telomere maintenance mechanism tumors and is associated with poorer survival. PLoS ONE 6(10):e26737. doi:10.1371/journal.pone.0026737 PubMedCentralPubMedCrossRef Royds JA, Al Nadaf S, Wiles AK, Chen YJ, Ahn A, Shaw A, Bowie S, Lam F, Baguley BC, Braithwaite AW, MacFarlane MR, Hung NA, Slatter TL (2011) The CDKN2A G500 allele is more frequent in GBM patients with no defined telomere maintenance mechanism tumors and is associated with poorer survival. PLoS ONE 6(10):e26737. doi:10.​1371/​journal.​pone.​0026737 PubMedCentralPubMedCrossRef
38.
go back to reference Yi X, Tesmer VM, Savre-Train I, Shay JW, Wright WE (1999) Both transcriptional and posttranscriptional mechanisms regulate human telomerase template RNA levels. Mol Cell Biol 19(6):3989–3997PubMedCentralPubMed Yi X, Tesmer VM, Savre-Train I, Shay JW, Wright WE (1999) Both transcriptional and posttranscriptional mechanisms regulate human telomerase template RNA levels. Mol Cell Biol 19(6):3989–3997PubMedCentralPubMed
39.
go back to reference Natarajan M, Mohan S, Konopinski R, Otto RA, Herman TS (2008) Induced telomerase activity in primary aortic endothelial cells by low-LET gamma-radiation is mediated through NF-kappaB activation. Br J Radiol 81(969):711–720. doi:10.1259/bjr/57867919 PubMedCrossRef Natarajan M, Mohan S, Konopinski R, Otto RA, Herman TS (2008) Induced telomerase activity in primary aortic endothelial cells by low-LET gamma-radiation is mediated through NF-kappaB activation. Br J Radiol 81(969):711–720. doi:10.​1259/​bjr/​57867919 PubMedCrossRef
40.
go back to reference Ram R, Uziel O, Eldan O, Fenig E, Beery E, Lichtenberg S, Nordenberg Y, Lahav M (2009) Ionizing radiation up-regulates telomerase activity in cancer cell lines by post-translational mechanism via ras/phosphatidylinositol 3-kinase/Akt pathway. Clin Cancer Res 15(3):914–923. doi:10.1158/1078-0432.CCR-08-0792 PubMedCrossRef Ram R, Uziel O, Eldan O, Fenig E, Beery E, Lichtenberg S, Nordenberg Y, Lahav M (2009) Ionizing radiation up-regulates telomerase activity in cancer cell lines by post-translational mechanism via ras/phosphatidylinositol 3-kinase/Akt pathway. Clin Cancer Res 15(3):914–923. doi:10.​1158/​1078-0432.​CCR-08-0792 PubMedCrossRef
42.
go back to reference Asai A, Oshima Y, Yamamoto Y, Uochi TA, Kusaka H, Akinaga S, Yamashita Y, Pongracz K, Pruzan R, Wunder E, Piatyszek M, Li S, Chin AC, Harley CB, Gryaznov S (2003) A novel telomerase template antagonist (GRN163) as a potential anticancer agent. Cancer Res 63(14):3931–3939PubMed Asai A, Oshima Y, Yamamoto Y, Uochi TA, Kusaka H, Akinaga S, Yamashita Y, Pongracz K, Pruzan R, Wunder E, Piatyszek M, Li S, Chin AC, Harley CB, Gryaznov S (2003) A novel telomerase template antagonist (GRN163) as a potential anticancer agent. Cancer Res 63(14):3931–3939PubMed
43.
go back to reference Tabori U, Ma J, Carter M, Zielenska M, Rutka J, Bouffet E, Bartels U, Malkin D, Hawkins C (2006) Human telomere reverse transcriptase expression predicts progression and survival in pediatric intracranial ependymoma. J Clin Oncol 24(10):1522–1528. doi:10.1200/JCO.2005.04.2127 PubMedCrossRef Tabori U, Ma J, Carter M, Zielenska M, Rutka J, Bouffet E, Bartels U, Malkin D, Hawkins C (2006) Human telomere reverse transcriptase expression predicts progression and survival in pediatric intracranial ependymoma. J Clin Oncol 24(10):1522–1528. doi:10.​1200/​JCO.​2005.​04.​2127 PubMedCrossRef
44.
go back to reference Hiyama E, Yamaoka H, Matsunaga T, Hayashi Y, Ando H, Suita S, Horie H, Kaneko M, Sasaki F, Hashizume K, Nakagawara A, Ohnuma N, Yokoyama T (2004) High expression of telomerase is an independent prognostic indicator of poor outcome in hepatoblastoma. Br J Cancer 91(5):972–979. doi:10.1038/sj.bjc.6602054 PubMedCentralPubMed Hiyama E, Yamaoka H, Matsunaga T, Hayashi Y, Ando H, Suita S, Horie H, Kaneko M, Sasaki F, Hashizume K, Nakagawara A, Ohnuma N, Yokoyama T (2004) High expression of telomerase is an independent prognostic indicator of poor outcome in hepatoblastoma. Br J Cancer 91(5):972–979. doi:10.​1038/​sj.​bjc.​6602054 PubMedCentralPubMed
45.
go back to reference Poremba C, Hero B, Heine B, Scheel C, Schaefer KL, Christiansen H, Berthold F, Kneif S, Stein H, Juergens H, Boecker W, Dockhorn-Dworniczak B (2000) Telomerase is a strong indicator for assessing the proneness to progression in neuroblastomas. Med Pediatr Oncol 35(6):651–655PubMedCrossRef Poremba C, Hero B, Heine B, Scheel C, Schaefer KL, Christiansen H, Berthold F, Kneif S, Stein H, Juergens H, Boecker W, Dockhorn-Dworniczak B (2000) Telomerase is a strong indicator for assessing the proneness to progression in neuroblastomas. Med Pediatr Oncol 35(6):651–655PubMedCrossRef
46.
go back to reference Dome JS, Chung S, Bergemann T, Umbricht CB, Saji M, Carey LA, Grundy PE, Perlman EJ, Breslow NE, Sukumar S (1999) High telomerase reverse transcriptase (hTERT) messenger RNA level correlates with tumor recurrence in patients with favorable histology Wilms’ tumor. Cancer Res 59(17):4301–4307PubMed Dome JS, Chung S, Bergemann T, Umbricht CB, Saji M, Carey LA, Grundy PE, Perlman EJ, Breslow NE, Sukumar S (1999) High telomerase reverse transcriptase (hTERT) messenger RNA level correlates with tumor recurrence in patients with favorable histology Wilms’ tumor. Cancer Res 59(17):4301–4307PubMed
47.
go back to reference Poremba C, Scheel C, Hero B, Christiansen H, Schaefer KL, Nakayama J, Berthold F, Juergens H, Boecker W, Dockhorn-Dworniczak B (2000) Telomerase activity and telomerase subunits gene expression patterns in neuroblastoma: a molecular and immunohistochemical study establishing prognostic tools for fresh-frozen and paraffin-embedded tissues. J Clin Oncol 18(13):2582–2592PubMed Poremba C, Scheel C, Hero B, Christiansen H, Schaefer KL, Nakayama J, Berthold F, Juergens H, Boecker W, Dockhorn-Dworniczak B (2000) Telomerase activity and telomerase subunits gene expression patterns in neuroblastoma: a molecular and immunohistochemical study establishing prognostic tools for fresh-frozen and paraffin-embedded tissues. J Clin Oncol 18(13):2582–2592PubMed
Metadata
Title
Prognostic significance of telomere maintenance mechanisms in pediatric high-grade gliomas
Authors
Kathleen Dorris
Matthew Sobo
Arzu Onar-Thomas
Eshini Panditharatna
Charles B. Stevenson
Sharon L. Gardner
Mariko D. DeWire
Christopher R. Pierson
Randal Olshefski
Sandra A. Rempel
Stewart Goldman
Lili Miles
Maryam Fouladi
Rachid Drissi
Publication date
01-03-2014
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 1/2014
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-014-1374-9

Other articles of this Issue 1/2014

Journal of Neuro-Oncology 1/2014 Go to the issue