nach oben

Erschienen in:

01.05.2010 | Laboratory Investigation - Human/Animal Tissue

Prognostic value of O⁶-methylguanine-DNA methyltransferase status in glioblastoma patients, assessed by five different methods

verfasst von: Lucie Karayan-Tapon, Véronique Quillien, Joëlle Guilhot, Michel Wager, Gaëlle Fromont, Stephan Saikali, Amandine Etcheverry, Abderrahmane Hamlat, Delphine Loussouarn, Loïc Campion, Mario Campone, François-Marie Vallette, Catherine Gratas-Rabbia-Ré

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2010

Einloggen, um Zugang zu erhalten

Abstract

This multicenter study assesses the value of O⁶-methylguanine-DNA methyltransferase (MGMT) status for predicting overall survival in glioblastoma patients. Five methods are used, to identify the approach with the best prognostic value. Eighty-one tumors were obtained from patients with glioblastomas treated by surgery and radiotherapy with concomitant temozolomide (TMZ) followed by adjuvant TMZ. MGMT promoter methylation was assessed by qualitative methyl-specific polymerase chain reaction (MSP), semiquantitative methyl-specific polymerase chain reaction (SQ-MSP), and pyrosequencing, while MGMT expression was measured at the RNA level by quantitative real-time PCR (Q-RT-PCR) and at the protein level by immunohistochemistry (IHC). MGMT promoter methylation as evaluated by MSP, SQ-MSP, and pyrosequencing was significantly correlated with overall survival. The best predictive value was obtained by pyrosequencing of one specific CpG position. Overall survival was 14 and 25 months for patients with percentages of methylation below and above the median, respectively. In contrast, MGMT status determined by Q-RT-PCR and IHC showed little or no correlation with overall survival, respectively. These results confirm the prognostic value of MGMT promoter methylation in glioblastoma patients initially treated with TMZ. SQ-MSP allowed better discrimination than classical MSP, and pyrosequencing represented a good option.

Nur mit Berechtigung zugänglich

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMed

Drablos F, Feyzi E, Aas PA, Vaagbo CB, Kavli B, Bratlie MS, Pena-Diaz J, Otterlei M, Slupphaug G, Krokan HE (2004) Alkylation damage in DNA and RNA—repair mechanisms and medical significance. DNA Repair (Amst) 3:1389–1407. doi:10.1016/j.dnarep.2004.05.004 CrossRef

Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343:1350–1354CrossRefPubMed

Criniere E, Kaloshi G, Laigle-Donadey F, Lejeune J, Auger N, Benouaich-Amiel A, Everhard S, Mokhtari K, Polivka M, Delattre JY, Hoang-Xuan K, Thillet J et al (2007) MGMT prognostic impact on glioblastoma is dependent on therapeutic modalities. J Neurooncol 83:173–179. doi:10.1007/s11060-006-9320-0 CrossRefPubMed

Donson AM, Addo-Yobo SO, Handler MH, Gore L, Foreman NK (2007) MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma. Pediatr Blood Cancer 48:403–407. doi:10.1002/pbc.20803 CrossRefPubMed

Hegi ME, Diserens AC, Godard S, Dietrich PY, Regli L, Ostermann S, Otten P, Van Melle G, de Tribolet N, Stupp R (2004) Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res 10:1871–1874CrossRefPubMed

Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003CrossRefPubMed

Watanabe T, Katayama Y, Komine C, Yoshino A, Ogino A, Ohta T, Fukushima T (2005) O⁶-Methylguanine-DNA methyltransferase methylation and TP53 mutation in malignant astrocytomas and their relationships with clinical course. Int J Cancer 113:581–587. doi:10.1002/ijc.20625 CrossRefPubMed

Eoli M, Menghi F, Bruzzone MG, De Simone T, Valletta L, Pollo B, Bissola L, Silvani A, Bianchessi D, D’Incerti L, Filippini G, Broggi G et al (2007) Methylation of O⁶-methylguanine DNA methyltransferase and loss of heterozygosity on 19q and/or 17p are overlapping features of secondary glioblastomas with prolonged survival. Clin Cancer Res 13:2606–2613CrossRefPubMed

10.

Paz MF, Yaya-Tur R, Rojas-Marcos I, Reynes G, Pollan M, Aguirre-Cruz L, Garcia-Lopez JL, Piquer J, Safont MJ, Balana C, Sanchez-Cespedes M, Garcia-Villanueva M et al (2004) CpG island hypermethylation of the DNA repair enzyme methyltransferase predicts response to temozolomide in primary gliomas. Clin Cancer Res 10:4933–4938CrossRefPubMed

11.

Balana C, Ramirez JL, Taron M, Roussos Y, Ariza A, Ballester R, Sarries C, Mendez P, Sanchez JJ, Rosell R (2003) O⁶-methyl-guanine-DNA methyltransferase methylation in serum and tumor DNA predicts response to 1,3-bis(2-chloroethyl)-1-nitrosourea but not to temozolomide plus cisplatin in glioblastoma multiforme. Clin Cancer Res 9:1461–1468PubMed

12.

Blanc JL, Wager M, Guilhot J, Kusy S, Bataille B, Chantereau T, Lapierre F, Larsen CJ, Karayan-Tapon L (2004) Correlation of clinical features and methylation status of MGMT gene promoter in glioblastomas. J Neurooncol 68:275–283. doi:10.1023/B:NEON.0000033385.37098.85 CrossRefPubMed

13.

Kamiryo T, Tada K, Shiraishi S, Shinojima N, Kochi M, Ushio Y (2004) Correlation between promoter hypermethylation of the O⁶-methylguanine-deoxyribonucleic acid methyltransferase gene and prognosis in patients with high-grade astrocytic tumors treated with surgery, radiotherapy, and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea-based chemotherapy. Neurosurgery 54:349–357CrossRefPubMed

14.

Gorlia T, van den Bent MJ, Hegi ME, Mirimanoff RO, Weller M, Cairncross JG, Eisenhauer E, Belanger K, Brandes AA, Allgeier A, Lacombe D, Stupp R (2008) Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. Lancet Oncol 9:29–38. doi:10.1016/S1470-2045(07)70384-4 CrossRefPubMed

15.

Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466. doi:10.1016/S1470-2045(09)70025-7 CrossRefPubMed

16.

Mineura K, Yanagisawa T, Watanabe K, Kowada M, Yasui N (1996) Human brain tumor O(6)-methylguanine-DNA methyltransferase mRNA and its significance as an indicator of selective chloroethylnitrosourea chemotherapy. Int J Cancer 69:420–425CrossRefPubMed

17.

Rolhion C, Penault-Llorca F, Kemeny JL, Kwiatkowski F, Lemaire JJ, Chollet P, Finat-Duclos F, Verrelle P (1999) O(6)-Methylguanine-DNA methyltransferase gene (MGMT) expression in human glioblastomas in relation to patient characteristics and p53 accumulation. Int J Cancer 84:416–420CrossRefPubMed

18.

Tanaka S, Kobayashi I, Utsuki S, Oka H, Fujii K, Watanabe T, Nagashima T, Hori T (2003) O⁶-Methylguanine-DNA methyltranspherase gene expression in gliomas by means of real-time quantitative RT-PCR and clinical response to nitrosoureas. Int J Cancer 103:67–72. doi:10.1002/ijc.10757 CrossRefPubMed

19.

Tanaka S, Kobayashi I, Utsuki S, Oka H, Yasui Y, Fujii K (2005) Down-regulation of O⁶-methylguanine-DNA methyltransferase gene expression in gliomas by platinum compounds. Oncol Rep 14:1275–1280PubMed

20.

Tanaka S, Oka H, Fujii K, Watanabe K, Nagao K, Kakimoto A (2005) Quantitation of O⁶-methylguanine-DNA methyltransferase gene messenger RNA in gliomas by means of real-time RT-PCR and clinical response to nitrosoureas. Cell Mol Neurobiol 25:1067–1071. doi:10.1007/s10571-005-8475-0 CrossRefPubMed

21.

Anda T, Shabani HK, Tsunoda K, Tokunaga Y, Kaminogo M, Shibata S, Hayashi T, Iseki M (2003) Relationship between expression of O⁶-methylguanine-DNA methyltransferase, glutathione-S-transferase pi in glioblastoma and the survival of the patients treated with nimustine hydrochloride: an immunohistochemical analysis. Neurol Res 25:241–248. doi:10.1179/016164103101201445 CrossRefPubMed

22.

Capper D, Mittelbronn M, Meyermann R, Schittenhelm J (2008) Pitfalls in the assessment of MGMT expression and in its correlation with survival in diffuse astrocytomas: proposal of a feasible immunohistochemical approach. Acta Neuropathol 115:249–259. doi:10.1007/s00401-007-0310-x CrossRefPubMed

23.

Chinot OL, Barrie M, Fuentes S, Eudes N, Lancelot S, Metellus P, Muracciole X, Braguer D, Ouafik L, Martin PM, Dufour H, Figarella-Branger D (2007) Correlation between O⁶-methylguanine-DNA methyltransferase and survival in inoperable newly diagnosed glioblastoma patients treated with neoadjuvant temozolomide. J Clin Oncol 25:1470–1475. doi:10.1200/JCO.2006.07.4807 CrossRefPubMed

24.

Nakasu S, Fukami T, Baba K, Matsuda M (2004) Immunohistochemical study for O⁶-methylguanine-DNA methyltransferase in the non-neoplastic and neoplastic components of gliomas. J Neurooncol 70:333–340. doi:10.1007/s11060-004-9170-6 CrossRefPubMed

25.

Pollack IF, Hamilton RL, Sobol RW, Burnham J, Yates AJ, Holmes EJ, Zhou T, Finlay JL (2006) O⁶-Methylguanine-DNA methyltransferase expression strongly correlates with outcome in childhood malignant gliomas: results from the CCG-945 Cohort. J Clin Oncol 24:3431–3437. doi:10.1200/JCO.2006.05.7265 CrossRefPubMed

26.

Rodriguez FJ, Thibodeau SN, Jenkins RB, Schowalter KV, Caron BL, O’Neill BP, David James C, Passe S, Slezak J, Giannini C (2008) MGMT immunohistochemical expression and promoter methylation in human glioblastoma. Appl Immunohistochem Mol Morphol 16:59–65PubMed

27.

Grasbon-Frodl EM, Kreth FW, Ruiter M, Schnell O, Bise K, Felsberg J, Reifenberger G, Tonn JC, Kretzschmar HA (2007) Intratumoral homogeneity of MGMT promoter hypermethylation as demonstrated in serial stereotactic specimens from anaplastic astrocytomas and glioblastomas. Int J Cancer 121:2458–2464. doi:10.1002/ijc.23020 CrossRefPubMed

28.

Preusser M, Janzer RC, Felsberg J, Reifenberger G, Hamou MF, Diserens AC, Stupp R, Gorlia T, Marosi C, Heinzl H, Hainfellner JA, Hegi M (2008) Anti-O⁶-methylguanine-methyltransferase (MGMT) immunohistochemistry in glioblastoma multiforme: observer variability and lack of association with patient survival impede its use as clinical biomarker. Brain Pathol 18:520–532. doi:10.1111/j.1750-3639.2008.00153.x PubMed

29.

Stupp R, Hegi ME (2007) Methylguanine methyltransferase testing in glioblastoma: when and how? J Clin Oncol 25:1459–1460. doi:10.1200/JCO.2006.09.7139 CrossRefPubMed

30.

Kagan J, Srivastava S, Barker PE, Belinsky SA, Cairns P (2007) Towards clinical application of methylated DNA sequences as cancer biomarkers: a joint NCI’s EDRN and NIST workshop on standards, methods, assays, reagents and tools. Cancer Res 67:4545–4549CrossRefPubMed

31.

Preusser M (2009) MGMT analysis at DNA, RNA and protein levels in glioblastoma tissue. Histol Histopathol 24:511–518PubMed

32.

Palmisano WA, Divine KK, Saccomanno G, Gilliland FD, Baylin SB, Herman JG, Belinsky SA (2000) Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res 60:5954–5958PubMed

33.

Fackler MJ, McVeigh M, Mehrotra J, Blum MA, Lange J, Lapides A, Garrett E, Argani P, Sukumar S (2004) Quantitative multiplex methylation-specific PCR assay for the detection of promoter hypermethylation in multiple genes in breast cancer. Cancer Res 64:4442–4452CrossRefPubMed

34.

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408. doi:10.1006/meth.2001.1262 CrossRefPubMed

35.

Concin N, Becker K, Slade N, Erster S, Mueller-Holzner E, Ulmer H, Daxenbichler G, Zeimet A, Zeillinger R, Marth C, Moll UM (2004) Transdominant DeltaTAp73 isoforms are frequently up-regulated in ovarian cancer. Evidence for their role as epigenetic p53 inhibitors in vivo. Cancer Res 64:2449–2460CrossRefPubMed

36.

Wager M, Guilhot J, Blanc JL, Ferrand S, Milin S, Bataille B, Lapierre F, Denis S, Chantereau T, Larsen CJ, Karayan-Tapon L (2006) Prognostic value of increase in transcript levels of Tp73 DeltaEx2-3 isoforms in low-grade glioma patients. Br J Cancer 95:1062–1069. doi:10.1038/sj.bjc.6603410 CrossRefPubMed

37.

Vlassenbroeck I, Califice S, Diserens AC, Migliavacca E, Straub J, Di Stefano I, Moreau F, Hamou MF, Renard I, Delorenzi M, Flamion B, DiGuiseppi J et al (2008) Validation of real-time methylation-specific PCR to determine O⁶-methylguanine-DNA methyltransferase gene promoter methylation in glioma. J Mol Diagn 10:332–337. doi:10.2353/jmoldx.2008.070169 CrossRefPubMed

38.

Nakagawachi T, Soejima H, Urano T, Zhao W, Higashimoto K, Satoh Y, Matsukura S, Kudo S, Kitajima Y, Harada H, Furukawa K, Matsuzaki H et al (2003) Silencing effect of CpG island hypermethylation and histone modifications on O⁶-methylguanine-DNA methyltransferase (MGMT) gene expression in human cancer. Oncogene 22:8835–8844. doi:10.1038/sj.onc.1207183 PubMed

39.

Brell M, Tortosa A, Verger E, Gil JM, Vinolas N, Villa S, Acebes JJ, Caral L, Pujol T, Ferrer I, Ribalta T, Graus F (2005) Prognostic significance of O⁶-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas. Clin Cancer Res 11:5167–5174CrossRefPubMed

40.

Cahill DP, Levine KK, Betensky RA, Codd PJ, Romany CA, Reavie LB, Batchelor TT, Futreal PA, Stratton MR, Curry WT, Iafrate AJ, Louis DN (2007) Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment. Clin Cancer Res 13:2038–2045CrossRefPubMed

41.

Grombacher T, Mitra S, Kaina B (1996) Induction of the alkyltransferase (MGMT) gene by DNA damaging agents and the glucocorticoid dexamethasone and comparison with the response of base excision repair genes. Carcinogenesis 17:2329–2336CrossRefPubMed

42.

Shen L, Kondo Y, Rosner GL, Xiao L, Hernandez NS, Vilaythong J, Houlihan PS, Krouse RS, Prasad AR, Einspahr JG, Buckmeier J, Alberts DS et al (2005) MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst 97:1330–1338. doi:10.1093/jnci/dji275 PubMedCrossRef

43.

Maxwell JA, Johnson SP, Quinn JA, McLendon RE, Ali-Osman F, Friedman AH, Herndon JE II, Bierau K, Bigley J, Bigner DD, Friedman HS (2006) Quantitative analysis of O⁶-alkylguanine-DNA alkyltransferase in malignant glioma. Mol Cancer Ther 5:2531–2539. doi:10.1158/1535-7163.MCT-06-0106 CrossRefPubMed

44.

Hattermann K, Mehdorn HM, Mentlein R, Schultka S, Held-Feindt J (2008) A methylation-specific and SYBR-green-based quantitative polymerase chain reaction technique for O(6)-methylguanine DNA methyltransferase promoter methylation analysis. Anal Biochem 377:62–71. doi:10.1016/j.ab.2008.03.014 CrossRefPubMed

45.

Tayrac MD, Etcheverry A, Aubry M, Saikali S, Hamlat A, Quillien V, Treut AL, Galibert MD, Mosser J (2008) Integrative genome-wide analysis reveals a robust genomic glioblastoma signature associated with copy number driving changes in gene expression. Genes Chromosomes Cancer 48:55–68. doi:10.1002/gcc.20618 CrossRef

46.

Mikeska T, Bock C, El-Maarri O, Hubner A, Ehrentraut D, Schramm J, Felsberg J, Kahl P, Buttner R, Pietsch T, Waha A (2007) Optimization of quantitative MGMT promoter methylation analysis using pyrosequencing and combined bisulfite restriction analysis. J Mol Diagn 9:368–381. doi:10.2353/jmoldx.2007.060167 CrossRefPubMed

47.

Dunn J, Baborie A, Alam F, Joyce K, Moxham M, Sibson R, Crooks D, Husband D, Shenoy A, Brodbelt A, Wong H, Liloglou T, Haylock B, Walker C (2009) Extent of MGMT promoter methylation correlates with outcome in glioblastomas given temozolomide and radiotherapy. Br J Cancer 16:1–8. doi:10.1038/sj.bjc.6605127 CrossRef

Titel: Prognostic value of O6-methylguanine-DNA methyltransferase status in glioblastoma patients, assessed by five different methods
verfasst von: Lucie Karayan-Tapon
Véronique Quillien
Joëlle Guilhot
Michel Wager
Gaëlle Fromont
Stephan Saikali
Amandine Etcheverry
Abderrahmane Hamlat
Delphine Loussouarn
Loïc Campion
Mario Campone
François-Marie Vallette
Catherine Gratas-Rabbia-Ré
Publikationsdatum: 01.05.2010
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 3/2010
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-009-0031-1

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

Springer Medizin

Prognostic value of O⁶-methylguanine-DNA methyltransferase status in glioblastoma patients, assessed by five different methods

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

Springer Medizin

Abstract

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

Weitere Artikel der Ausgabe 3/2010

Hepatocyte growth factor in cerebrospinal fluid is associated with mortality and recurrence of glioblastoma, and could be of prognostic value

Primary CNS lymphoma in the elderly: temozolomide therapy and MGMT status

Activated EGFR signaling increases proliferation, survival, and migration and blocks neuronal differentiation in post-natal neural stem cells

Multiple extracranial metastases from secondary glioblastoma multiforme: a case report and review of the literature

Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites

Specific chromosomal imbalances as detected by array CGH in ependymomas in association with tumor location, histological subtype and grade

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