Prognosis of glioblastoma with faint MGMT methylation-specific PCR product

详细信息    查看全文

• 作者：Chih-Yi Hsu ; Hsiang-Ling Ho ; Shih-Chieh Lin…
• 关键词：Glioblastoma ; MGMT ; Methylation ; PCR ; Quality control ; Prognosis
• 刊名：Journal of Neuro-Oncology
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：122
• 期：1
• 页码：179-188
• 全文大小：369 KB
• 参考文献：1. Stupp, R, Hegi, ME, Mason, WP, Bent, MJ, Taphoorn, MJ, Janzer, RC, Ludwin, SK, Allgeier, A, Fisher, B, Belanger, K, Hau, P, Brandes, AA, Gijtenbeek, J, Marosi, C, Vecht, CJ, Mokhtari, K, Wesseling, P, Villa, S, Eisenhauer, E, Gorlia, T, Weller, M, Lacombe, D, Cairncross, JG, Mirimanoff, RO (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: pp. 459-466 CrossRef
  2. Esteller, M, Hamilton, SR, Burger, PC, Baylin, SB, Herman, JG (1999) Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 59: pp. 793-797
  3. Everhard, S, Tost, J, Abdalaoui, H, Criniere, E, Busato, F, Marie, Y, Gut, IG, Sanson, M, Mokhtari, K, Laigle-Donadey, F, Hoang-Xuan, K, Delattre, JY, Thillet, J (2009) Identification of regions correlating MGMT promoter methylation and gene expression in glioblastomas. Neuro Oncol 11: pp. 348-356 CrossRef
  4. Malley, DS, Hamoudi, RA, Kocialkowski, S, Pearson, DM, Collins, VP, Ichimura, K (2011) A distinct region of the MGMT CpG island critical for transcriptional regulation is preferentially methylated in glioblastoma cells and xenografts. Acta Neuropathol 121: pp. 651-661 CrossRef
  5. Vlassenbroeck, I, Califice, S, Diserens, AC, Migliavacca, E, Straub, J, Stefano, I, Moreau, F, Hamou, MF, Renard, I, Delorenzi, M, Flamion, B, DiGuiseppi, J, Bierau, K, Hegi, ME (2008) Validation of real-time methylation-specific PCR to determine O6-methylguanine-DNA methyltransferase gene promoter methylation in glioma. J Mol Diagn 10: pp. 332-337 CrossRef
  6. Karayan-Tapon, L, Quillien, V, Guilhot, J, Wager, M, Fromont, G, Saikali, S, Etcheverry, A, Hamlat, A, Loussouarn, D, Campion, L, Campone, M, Vallette, FM, Gratas-Rabbia-Re, C (2010) Prognostic value of O6-methylguanine-DNA methyltransferase status in glioblastoma patients, assessed by five different methods. J Neurooncol 97: pp. 311-322 CrossRef
  7. Christians, A, Hartmann, C, Benner, A, Meyer, J, Deimling, A, Weller, M, Wick, W, Weiler, M (2012) Prognostic value of three different methods of MGMT promoter methylation analysis in a prospective trial on newly diagnosed glioblastoma. PLoS One 7: pp. e33449 CrossRef
  8. Hegi, ME, Diserens, AC, Gorlia, T, Hamou, MF, Tribolet, N, Weller, M, Kros, JM, Hainfellner, JA, Mason, W, Mariani, L, Bromberg, JE, Hau, P, Mirimanoff, RO, Cairncross, JG, Janzer, RC, Stupp, R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352: pp. 997-1003 CrossRef
  9. Felsberg, J, Rapp, M, Loeser, S, Fimmers, R, Stummer, W, Goeppert, M, Steiger, HJ, Friedensdorf, B, Reifenberger, G, Sabel, MC (2009) Prognostic significance of molecular markers and extent of resection in primary glioblastoma patients. Clin Cancer Res 15: pp. 6683-6693 CrossRef
  10. Cao, VT, Jung, TY, Jung, S, Jin, SG, Moon, KS, Kim, IY, Kang, SS, Park, CS, Lee, KH, Chae, HJ (2009) The correlation and prognostic significance of MGMT promoter methylation and MGMT protein in glioblastomas. Neurosurgery 65: pp. 866-875 CrossRef
  11. 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: pp. 1350-1354 CrossRef
  12. Lechapt-Zalcman, E, Levallet, G, Dugue, AE, Vital, A, Diebold, MD, Menei, P, Colin, P, Peruzzy, P, Emery, E, Bernaudin, M, Chapon, F, Guillamo, JS (2012) O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation and low MGM
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7373

文摘

Methylation-specific polymerase chain reaction (MSP) for the promoter methylation status of O6-methylguanine-DNA-methyltranferase (MGMT) gene theoretically provides a positive or negative result. However, the faint MSP product is difficult to interpret. The aim of this study was to evaluate the significance of faint MSP product in glioblastoma (GBM). Critical concentrations of methylated control DNA, i.e., 100, 1, 0.5 and 0?% were run parallel with 116 newly diagnosed GBMs in order to standardize the interpretation and to distinguish positive (+), equivocal (±), and negative (? unmethylated) results. Cases with the faint MSP product and its intensity between those of 1 and 0.5?% DNA controls were considered equivocal (±). MGMT methylation quantifications were also determined by quantitative real-time MSP (qMSP) and pyrosequencing (PSQ), and protein expression was detected by immunohistochemistry. There were significant correlations between MSP and all the aforementioned studies. The concordance rates between the MSP+ and qMSP+ cases, as well as the MSP?and qMSP?cases were 100?%, and the MSP± cases comprised 76.5?% of qMSP+ cases and 23.5?% of qMSP?cases. PSQ study showed that heterogeneous methylation was more frequently encountered in the MSP± cases. Multivariate analyses disclosed that although the overall survival of the MSP± cases was indistinct from that of the MSP+ cases, its progression free survival was significantly worse and was indistinct from that of the MSP?cases. In conclusion, GBMs with faint MGMT MSP products should be distinguished from MSP+ cases as their behaviors were different.