nach oben

Erschienen in:

27.07.2016 | Laboratory Investigation

hTERT promoter methylation in meningiomas and central nervous hemangiopericytomas

verfasst von: Gina Fürtjes, Michaela Köchling, Susanne Peetz-Dienhart, Andrea Wagner, Katharina Heß, Martin Hasselblatt, Volker Senner, Walter Stummer, Werner Paulus, Benjamin Brokinkel

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2016

Einloggen, um Zugang zu erhalten

Abstract

In meningiomas, prognostic impact of mutations in the human telomerase reverse transcriptase (hTERT) promoter region was recently shown, while studies of promoter methylation and analyses of hemangiopericytomas are lacking. hTERT promoter methylation was analyzed in 78 meningioma and 38 meningeal hemangiopericytoma samples by methylation-specific polymerase chain reaction (MS-PCR) and compared with histopathological and clinical variables and with immunohistochemical hTERT expression. Promoter methylation was found in 62 samples (53 %) and tended to be higher in meningiomas (N = 19/41, 46 %) than in hemangiopericytomas (N = 8/33, 24 %, p = .057). In meningiomas, methylation was 16, 60 and 77 % in grade I, II and III tumors (p < .001) and higher in recurrent (N = 33/37, 89 %) than in primary diagnosed (N = 19/41, 46 %) tumors (OR 5.14, 95 % CI 1.34–19.71, p = .017). Univariate analyses showed shorter mean progression free and overall survival in methylated than in unmethylated individuals (26 vs. 100 months; p = .045 and 110 vs. 113 months; p = .025, respectively). Moreover, hTERT expression was found in 70 % (N = 53) and was more frequent in methylated than in unmethylated samples (78 vs. 52 %, OR 3.36, 95 % CI 1.20–9.40, p = .021). In hemangiopericytomas, methylation was similar in grade II (24 %) and III (25 %, p > .05) and in primary (24 %) and recurrent tumors (40 %, p > .05). hTERT expression was similar as compared to meningiomas (74 %, N = 28, p > .05) but was independent of promoter methylation (OR 4.26, 95 % CI 0.47–39.0, p = .199). In meningeal tumors, hTERT promoter methylation is more common than mutations and in meningiomas but not in hemangiopericytomas positively correlated with WHO grade and hTERT expression.

Kalala JP, Maes L, Vandenbroecke C, de Ridder L (2005) The hTERT protein as a marker for malignancy in meningiomas. Oncol Rep 13:273–277PubMed

Maes L, Kalala JP, Cornelissen R, de Ridder L (2006) Telomerase activity and hTERT protein expression in meningiomas: an analysis in vivo versus in vitro. Anticancer Res 26:2295–2300PubMed

Maes L, Lippens E, Kalala JP, de Ridder L (2005) The hTERT-protein and Ki-67 labelling index in recurrent and non-recurrent meningiomas. Cell Prolif 38:3–12. doi:10.1111/j.1365-2184.2005.00325.x CrossRefPubMed

Simon M, Park TW, Leuenroth S, Hans VH, Loning T, Schramm J (2000) Telomerase activity and expression of the telomerase catalytic subunit, hTERT, in meningioma progression. J Neurosurg 92:832–840. doi:10.3171/jns.2000.92.5.0832 CrossRefPubMed

Arita H, Narita Y, Fukushima S, Tateishi K, Matsushita Y, Yoshida A, Miyakita Y, Ohno M, Collins VP, Kawahara N, Shibui S, Ichimura K (2013) Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss. Acta Neuropathol 126:267–276. doi:10.1007/s00401-013-1141-6 CrossRefPubMed

Arita H, Narita Y, Takami H, Fukushima S, Matsushita Y, Yoshida A, Miyakita Y, Ohno M, Shibui S, Ichimura K (2013) TERT promoter mutations rather than methylation are the main mechanism for TERT upregulation in adult gliomas. Acta Neuropathol 126:939–941. doi:10.1007/s00401-013-1203-9 CrossRefPubMed

Killela PJ, Reitman ZJ, Jiao Y, Bettegowda C, Agrawal N, Diaz LA Jr, Friedman AH, Friedman H, Gallia GL, Giovanella BC, Grollman AP, He TC, He Y, Hruban RH, Jallo GI, Mandahl N, Meeker AK, Mertens F, Netto GJ, Rasheed BA, Riggins GJ, Rosenquist TA, Schiffman M, Shih Ie M, Theodorescu D, Torbenson MS, Velculescu VE, Wang TL, Wentzensen N, Wood LD, Zhang M, McLendon RE, Bigner DD, Kinzler KW, Vogelstein B, Papadopoulos N, Yan H (2013) TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci USA 110:6021–6026. doi:10.1073/pnas.1303607110 CrossRefPubMedPubMedCentral

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 24:1522–1528. doi:10.1200/JCO.2005.04.2127 CrossRefPubMed

Koelsche C, Sahm F, Capper D, Reuss D, Sturm D, Jones DT, Kool M, Northcott PA, Wiestler B, Bohmer K, Meyer J, Mawrin C, Hartmann C, Mittelbronn M, Platten M, Brokinkel B, Seiz M, Herold-Mende C, Unterberg A, Schittenhelm J, Weller M, Pfister S, Wick W, Korshunov A, von Deimling A (2013) Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system. Acta Neuropathol 126:907–915. doi:10.1007/s00401-013-1195-5 CrossRefPubMed

10.

Park CK, Lee SH, Kim JY, Kim JE, Kim TM, Lee ST, Choi SH, Park SH, Kim IH (2014) Expression level of hTERT is regulated by somatic mutation and common single nucleotide polymorphism at promoter region in glioblastoma. Oncotarget 5:3399–3407CrossRefPubMedPubMedCentral

11.

Huang DS, Wang Z, He XJ, Diplas BH, Yang R, Killela PJ, Meng Q, Ye ZY, Wang W, Jiang XT, Xu L, He XL, Zhao ZS, Xu WJ, Wang HJ, Ma YY, Xia YJ, Li L, Zhang RX, Jin T, Zhao ZK, Xu J, Yu S, Wu F, Liang J, Wang S, Jiao Y, Yan H, Tao HQ (2015) Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation. Eur J Cancer 51:969–976. doi:10.1016/j.ejca.2015.03.010 CrossRefPubMedPubMedCentral

12.

Goutagny S, Nault JC, Mallet M, Henin D, Rossi JZ, Kalamarides M (2014) High incidence of activating TERT promoter mutations in meningiomas undergoing malignant progression. Brain Pathol 24:184–189. doi:10.1111/bpa.12110 CrossRefPubMed

13.

Sahm F, Schrimpf D, Olar A, Koelsche C, Reuss D, Bissel J, Kratz A, Capper D, Schefzyk S, Hielscher T, Wang Q, Sulman EP, Adeberg S, Koch A, Okuducu AF, Brehmer S, Schittenhelm J, Becker A, Brokinkel B, Schmidt M, Ull T, Gousias K, Friederike A, Lamszus KK, Debus J, Mawrin C, Kim YJ, Simon M, Ketter R, Paulus W, Aldape KD, Herold-Mende C, von Deimling A (2016) TERT promoter mutations and risk of recurrence in meningioma. J Natl Cancer Inst 108. doi:10.1093/jnci/djv377

14.

Castelo-Branco P, Choufani S, Mack S, Gallagher D, Zhang C, Lipman T, Zhukova N, Walker EJ, Martin D, Merino D, Wasserman JD, Elizabeth C, Alon N, Zhang L, Hovestadt V, Kool M, Jones DT, Zadeh G, Croul S, Hawkins C, Hitzler J, Wang JC, Baruchel S, Dirks PB, Malkin D, Pfister S, Taylor MD, Weksberg R, Tabori U (2013) Methylation of the TERT promoter and risk stratification of childhood brain tumours: an integrative genomic and molecular study. Lancet Oncol 14:534–542. doi:10.1016/S1470-2045(13)70110-4 CrossRefPubMed

15.

Ruland V, Hartung S, Kordes U, Wolff JE, Paulus W, Hasselblatt M (2014) Methylation of the hTERT promoter is frequent in choroid plexus tumors but not of independent prognostic value. J Neurooncol 119:215–216. doi:10.1007/s11060-014-1473-7 CrossRefPubMed

16.

Kochling M, Ewelt C, Furtjes G, Peetz-Dienhart S, Koos B, Hasselblatt M, Paulus W, Stummer W, Brokinkel B (2016) hTERT promoter methylation in pituitary adenomas. Brain Tumor Pathol 33:27–34. doi:10.1007/s10014-015-0230-8 CrossRefPubMed

17.

Perry A, Louis DN, Scheithauer BW, Budka H, von Deimling A (2007) Meningiomas. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumors of the central nervous system, 4 edn. International agency on cancer research, Lyon, pp 164–172

18.

Paulus W, Scheithauer BW, Perry A (2007) Mesenchymal, non-meningothelial tumours. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO Classification of tumors of the central nervous System, 4 edn. International agency on cancer research, Lyon, pp 173–177

19.

Maes L, Kalala JP, Cornelissen M, de Ridder L (2007) Progression of astrocytomas and meningiomas: an evaluation in vitro. Cell Prolif 40:14–23. doi:10.1111/j.1365-2184.2007.00415.x CrossRefPubMed

20.

Boldrini L, Pistolesi S, Gisfredi S, Ursino S, Lupi G, Caniglia M, Pingitore R, Basolo F, Parenti G, Fontanini G (2003) Telomerase in intracranial meningiomas. Int J Mol Med 12:943–947PubMed

21.

Maes L, Van Neste L, Van Damme K, Kalala JP, De Ridder L, Bekaert S, Cornelissen M (2007) Relation between telomerase activity, hTERT and telomere length for intracranial tumours. Oncol Rep 18:1571–1576PubMed

22.

Chen HJ, Liang CL, Lu K, Lin JW, Cho CL (2000) Implication of telomerase activity and alternations of telomere length in the histologic characteristics of intracranial meningiomas. Cancer 89:2092–2098CrossRefPubMed

23.

Leuraud P, Dezamis E, Aguirre-Cruz L, Taillibert S, Lejeune J, Robin E, Mokhtari K, Boch AL, Cornu P, Delattre JY, Sanson M (2004) Prognostic value of allelic losses and telomerase activity in meningiomas. J Neurosurg 100:303–309. doi:10.3171/jns.2004.100.2.0303 CrossRefPubMed

24.

Langford LA, Piatyszek MA, Xu R, Schold SC Jr, Wright WE, Shay JW (1997) Telomerase activity in ordinary meningiomas predicts poor outcome. Hum Pathol 28:416–420CrossRefPubMed

25.

Simon M, Park TW, Koster G, Mahlberg R, Hackenbroch M, Bostrom J, Loning T, Schramm J (2001) Alterations of INK4a(p16-p14ARF)/INK4b(p15) expression and telomerase activation in meningioma progression. J Neurooncol 55:149–158CrossRefPubMed

26.

Cai J, Yang P, Zhang C, Zhang W, Liu Y, Bao Z, Liu X, Du W, Wang H, Jiang T, Jiang C (2014) ATRX mRNA expression combined with IDH1/2 mutational status and Ki-67 expression refines the molecular classification of astrocytic tumors: evidence from the whole transcriptome sequencing of 169 samples samples. Oncotarget 5:2551–2561CrossRefPubMedPubMedCentral

27.

Dorris K, Sobo M, Onar-Thomas A, Panditharatna E, Stevenson CB, Gardner SL, Dewire MD, Pierson CR, Olshefski R, Rempel SA, Goldman S, Miles L, Fouladi M, Drissi R (2014) Prognostic significance of telomere maintenance mechanisms in pediatric high-grade gliomas. J Neurooncol 117:67–76. doi:10.1007/s11060-014-1374-9 CrossRefPubMedPubMedCentral

28.

Nguyen DN, Heaphy CM, de Wilde RF, Orr BA, Odia Y, Eberhart CG, Meeker AK, Rodriguez FJ (2013) Molecular and morphologic correlates of the alternative lengthening of telomeres phenotype in high-grade astrocytomas. Brain Pathol 23:237–243. doi:10.1111/j.1750-3639.2012.00630.x CrossRefPubMed

29.

Wiestler B, Capper D, Holland-Letz T, Korshunov A, von Deimling A, Pfister SM, Platten M, Weller M, Wick W (2013) ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with better prognosis. Acta Neuropathol 126:443–451. doi:10.1007/s00401-013-1156-z CrossRefPubMed

30.

Estey EH (2013) Epigenetics in clinical practice: the examples of azacitidine and decitabine in myelodysplasia and acute myeloid leukemia. Leukemia 27:1803–1812. doi:10.1038/leu.2013.173 CrossRefPubMed

31.

Pettigrew KA, Armstrong RN, Colyer HA, Zhang SD, Rea IM, Jones RE, Baird DM, Mills KI (2012) Differential TERT promoter methylation and response to 5-aza-2′-deoxycytidine in acute myeloid leukemia cell lines: TERT expression, telomerase activity, telomere length, and cell death. Genes Chromosomes Cancer 51:768–780. doi:10.1002/gcc.21962 CrossRefPubMed

32.

Zhang X, Li B, de Jonge N, Bjorkholm M, Xu D (2015) The DNA methylation inhibitor induces telomere dysfunction and apoptosis of leukemia cells that is attenuated by telomerase over-expression. Oncotarget 6:4888–4900. doi:10.18632/oncotarget.2917 CrossRefPubMedPubMedCentral

33.

Hajek M, Votruba I, Holy A, Krecmerova M, Tloust’ova E (2008) Alpha anomer of 5-aza-2′-deoxycytidine down-regulates hTERT mRNA expression in human leukemia HL-60 cells. Biochem Pharmacol 75:965–972. doi:10.1016/j.bcp.2007.10.018 CrossRefPubMed

34.

Grandjenette C, Schnekenburger M, Karius T, Ghelfi J, Gaigneaux A, Henry E, Dicato M, Diederich M (2014) 5-aza-2′-deoxycytidine-mediated c-myc down-regulation triggers telomere-dependent senescence by regulating human telomerase reverse transcriptase in chronic myeloid leukemia. Neoplasia 16:511–528. doi:10.1016/j.neo.2014.05.009 CrossRefPubMedPubMedCentral

35.

Wu YL, Dudognon C, Nguyen E, Hillion J, Pendino F, Tarkanyi I, Aradi J, Lanotte M, Tong JH, Chen GQ, Segal-Bendirdjian E (2006) Immunodetection of human telomerase reverse-transcriptase (hTERT) re-appraised: nucleolin and telomerase cross paths. J Cell Sci 119:2797–2806CrossRefPubMed

Titel: hTERT promoter methylation in meningiomas and central nervous hemangiopericytomas
verfasst von: Gina Fürtjes
Michaela Köchling
Susanne Peetz-Dienhart
Andrea Wagner
Katharina Heß
Martin Hasselblatt
Volker Senner
Walter Stummer
Werner Paulus
Benjamin Brokinkel
Publikationsdatum: 27.07.2016
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 1/2016
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-016-2226-6

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

23.04.2024 | Demenz | Nachrichten

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

hTERT promoter methylation in meningiomas and central nervous hemangiopericytomas

Abstract

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Hustenstiller lindert Agitation bei Alzheimer

Update Neurologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2016

Treatment of pediatric cerebral radiation necrosis: a systematic review

Prognostic role of microRNA-21 expression in gliomas: a meta-analysis

Inhibition of STAT3 enhances the radiosensitizing effect of temozolomide in glioblastoma cells in vitro and in vivo

The role of AKT isoforms in glioblastoma: AKT3 delays tumor progression

Phase I trial of dose-escalating metronomic temozolomide plus bevacizumab and bortezomib for patients with recurrent glioblastoma

Stereotactic brachytherapy using iodine 125 seeds for the treatment of primary and recurrent anaplastic glioma WHO° III

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Hustenstiller lindert Agitation bei Alzheimer

Update Neurologie