The correlation and prognostic significance of MGMT promoter methylation and MGMT protein in glioblastomas

Neurosurgery

Volumn 65, Issue 5, 2009, Pages 866-875

  Cao, Van Thang ^a   Jung, Tae Young ^a   Jung, Shin ^a   Jin, Shu Guang ^a   Moon, Kyung Sub ^a   Kim, In Young ^a   Kang, Sam Suk ^a   Park, Chang Soo ^a   Lee, Kyung Hwa ^a   Chae, Hong Jae ^a  

^a Chonnam National University   (South Korea)

Author keywords

Chemotherapy; Glioblastoma; Immunohistochemistry; MGMT promoter methylation; MGMT protein

Indexed keywords

METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE; TEMOZOLOMIDE;

ADOLESCENT; ADULT; AGED; ARTICLE; BRAIN BIOPSY; CANCER CHEMOTHERAPY; CONTROLLED STUDY; CORRELATION ANALYSIS; FEMALE; GLIOBLASTOMA; HUMAN; IMMUNOHISTOCHEMISTRY; KARNOFSKY PERFORMANCE STATUS; MAJOR CLINICAL STUDY; MALE; MULTIVARIATE ANALYSIS; NEUROSURGERY; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROGNOSIS; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN METHYLATION; STATISTICAL SIGNIFICANCE; SURGICAL APPROACH; SURVIVAL TIME;

ADOLESCENT; ADULT; AGED; ANTINEOPLASTIC AGENTS, ALKYLATING; BRAIN NEOPLASMS; COMBINED MODALITY THERAPY; DACARBAZINE; DNA METHYLATION; DNA MODIFICATION METHYLASES; DNA REPAIR ENZYMES; FEMALE; GENE EXPRESSION; GLIOBLASTOMA; HUMANS; IMMUNOHISTOCHEMISTRY; KAPLAN-MEIERS ESTIMATE; MALE; MIDDLE AGED; POLYMERASE CHAIN REACTION; PROGNOSIS; PROMOTER REGIONS, GENETIC; RADIOTHERAPY; TUMOR SUPPRESSOR PROTEINS; YOUNG ADULT;

EID: 70350314719     PISSN: 0148396X     EISSN: None     Source Type: Journal    
DOI: 10.1227/01.NEU.0000357325.90347.A1     Document Type: Article

References (47)

1. Allay E, Veigl M, Gerson SL: Mice over-expressing human O6 alkylguanine-DNA alkyltransferase selectively reduce O6 methylguanine mediated carcinogenic mutations to threshold levels after n-methyl-n-nitrosourea. Oncogene 18:3783-3787, 1999.
2. Ammirati M, Vick N, Liao YL, Ciric I, Mikhael M: Effect of the extent of surgical resection on survival and quality of life in patients with supratentorial glioblastomas and anaplastic astrocytomas. Neurosurgery 21:201-206, 1987.
3. Bae SI, Lee HS, Kim SH, Kim WH: Inactivation of O6-methylguanine-DNA methyltransferase by promoter CpG island hypermethylation in gastric cancers. Br J Cancer 86:1888-1892, 2002.
4. Baylin SB, Herman JG: DNA hypermethylation in tumorigenesis: Epigenetic joins genetics. Trends Genet 16:168-174, 2000.
5. Bhakat KK, Mitra S: Regulation of the human O6-methylguanine-DNA methyltransferase gene by transcriptional co-activators cAMP response element-binding protein-binding protein and p300. J Biol Chem 275:34197-34204, 2000.
6. Bhakat KK, Mitra S: CpG methylation-dependent repression of the human O6-methylguanine-DNA methyltransferase gene linked to chromatin structure alteration. Carcinogenesis 24:1337-1345, 2003.
7. Blanc JL, Wager M, Guilhot J, Kusy S, Bataille B, Chantereau T, Lapierre F, Larsen CJ, Karayan-Tapon L: Correlation of clinical features and methylation status of MGMT gene promoter in glioblastomas. J Neurooncol 68:275-283, 2004.
8. Blough MD, Zlatescu MC, Cairncross JG: O6-methylguanine-DNA methyltransferase regulation by p53 in astrocytic cells. Cancer Res 67:580-584, 2007.
9. Brell M, Tortosa A, Verger E, Gil JM, Viñolas N, Villá S, Acebes JJ, Caral L, Pujol T, Ferrer I, Ribalta T, Graus F: Prognostic significance of O6-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas. Clin Cancer Res 11, 5167-5174, 2005.
10. Cameron EE, Baylin SB, Herman JG: p15 (ink4b) CpG island methylation in primary acute leukemia is heterogeneous and suggests density as a critical factor for transcriptional silencing. Blood 94:2445-2451, 1999.
11. Cavenee WK, Furnari FB, Nagane M: Astrocytic tumors, in Kleihues P, Cavenee WK (eds): Pathology and Genetics: Tumours of the Nervous System. Lyon, IARC Press, 2000, vol 26, pp 27-29.
12. Costello JF, Futscher BW, Tano K, Graunke DM, Pieper RO: Graded methylation in the promoter and in the body of the O6-methylguanine-DNA methyltransferase gene correlates with MGMT expression in human glioma cells. J Biol Chem 269:17228-17237, 1994.
13. Crinière 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, Sanson M: MGMT prognostic impact on glioblastoma is dependent on therapeutic modalities. J Neurooncol 83:173-179, 2007.
14. Curran WJ Jr, Scott CB, Horton J, Nelson JS, Weinstein AS, Fischbach AJ, Chang CH, Rotman M, Asbell SO, Krisch RE: Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst 85:704-710, 1993.
15. Derks S, Lentjes MH, Hellebrekers DM, de Bruïne AP, Herman JG, van Engeland M: Methylation-specific PCR unraveled. Cell Oncol 26:291-299, 2004.
16. Esteller M, Herman JG: Generating mutations but providing chemosensitivity: The role of O6-methylguanine DNA methyltransferase in human cancer. Oncogene 23:1-8. 2004.
17. Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG: Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343:1350-1354, 2000.
18. Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG: Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 59:793-797, 1999.
19. Esteller M, Risques RA, Toyota M, Capella G, Moreno V, Peinado MA, Baylin SB, Herman JH: Promoter hypermethylation of the DNA repair gene O6-methylguanine-DNA methyltransferase is associated with the presence of G:C to A:T transition mutations in p53 in human colorectal tumorigenesis. Cancer Res 61:4689-4692, 2001.
20. Esteller M, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA, Watkins DN, Issa JP, Sidransky D, Baylin SB, Herman JG: Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is associated with G to A mutations in K-ras in colorectal tumorigenesis. Cancer Res 60:2368-2371, 2000.
21. Friedman HS, McLendon RE, Kerby T, Dugan M, Bigner SH, Henry AJ, Ashley DM, Krischer J, Lovell S, Rasheed K, Marchev F, Seman AJ, Cokgor I, Rich J, Stewart E, Colvin OM, Provenzale JM, Bigner DD, Haglund MM, Friedman AH, Modrich PL: DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma. J Clin Oncol 16:3851-3857, 1998.
22. Gerson SL: MGMT: Its role in cancer aetiology and cancer therapeutics. Nat Rev Cancer 4:296-307, 2004.
23. Goth R, Rajewsky MF: Persistence of O6-ethylguanine in rat brain DNA: Correlation with nervous-system-specific carcinogenesis by ethylnitrosourea. Proc Natl Acad Sci U S A 71:639-643, 1974.
24. Grasbon-Frodl EM, Kreth FW, Ruiter M, Schnell O, Bise K, Felsberg J, Reifenberger G, Tonn JC, Kretzschmar HA: Intratumoral homogeneity of MGMT promoter hypermethylation as demonstrated in serial stereotactic specimens from anaplastic astrocytomas and glioblastomas. Int J Cancer 121:2458-2464, 2007.
25. Harris LC, Potter PM, Tano K, Shiota S, Mitra S, Brent TP: Characterization of the promoter region of the human O6-methylguanine-DNA methyltransferase gene. Nucleic Acids Res 19:6163-6167, 1991.
26. Harris LC, Remack JS, Brent TP: Identification of a 59 bp enhancer located at the first exon/intron boundary of the human O6-methylguanine DNA methyltransferase gene. Nucleic Acids Res 22:4614-4619, 1994.
27. Hegi ME, Diserens AC, Godard S, Dietrich PY, Regli L, Osermann S, Otten P, Van Melle G, de Tribolet N, Stubb R: Clinical trial substantiates the predictive value of O6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res 10:1871-1874, 2004.
28. 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, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997-1003, 2005.
29. Herman JG, Graff JR, Myöhänen S, Nelkin BD, Baylin SB: Methylation-specific PCR: A novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A 93:9821-9826, 1996.
30. Jaeckle KA, Eyre HJ, Townsend JJ, Schulman S, Knudson HM, Belanich M, Yarosh DB, Bearman SI, Giroux DJ, Schold SC: Correlation of tumor O6-methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: A Southwest Oncology Group study. J Clin Oncol 16:3310-3315, 1998.
31. Komine C, Watanabe T, Katayama Y, Yoshino A, Yokoyama T, Fukushima T: Promoter hypermethylation of the DNA repair gene O6-methylguanine-DNA methyltransferase is an independent predictor of shortened progression free survival in patients with low-grade diffuse astrocytomas. Brain Pathol 13:176-184, 2003.
32. Lavon I, Fuchs D, Zrihan D, Efroni G, Zelikovitch B, Fellig Y, Siegal T: Novel mechanism whereby nuclear factor kb mediates DNA damage repair through regulation of O6-methylguanine-DNA-methyltransferase. Cancer Res 67:8952-8959, 2007.
33. Liu L, Allay E, Dumenco LL, Gerson SL: Rapid repair of O6-methylguanine-DNA adducts protects transgenic mice from methylnitrosourea- induced thymic lymphomas. Cancer Res 54:4648-4652, 1994.
34. Margison GP, Povey AC, Kaina B, Santibáñez Koref MF: Variability and regulation of O6-alkylguanine-DNA alkyltransferase. Carcinogenesis 24:625-635, 2003.
35. McCabe MT, Low JA, Daignault S, Imperiale MJ, Wojno KJ, Day ML: Inhibition of DNA methyltransferase activity prevents tumorigenesis in a mouse model of prostate cancer. Cancer Res 66:385-392, 2006.
36. Nakasu S, Fukami T, Baba K, Matsuda M: Immunohistochemical study for O6-methylguanine-DNA methyltransferase in the non-neoplastic and neoplastic components of gliomas. J Neurooncol 70:333-340, 2004.
37. Park TJ, Han SU, Cho YK, Paik WK, Kim YB, Lim IK: Methylation of O6-methylguanine-DNA methyltransferase gene is associated significantly with k-ras mutation, lymph node invasion, tumor staging, and disease free survival in patients with gastric carcinoma. Cancer 92:2760-2768, 2002.
38. Paz MF, Fraga MF, Avila S, Guo M, Pollan M, Herman JG, Esteller M: A systematic profile of DNA methylation in human cancer cell lines. Cancer Res 63:1114-1121, 2003. (Pubitemid 36278446)
39. Paz MF, Yaya-Tur R, Rojas-Marcos I, Reynes G, Pollan M, Aguirre-Cruz L, García-Lopez JL, Piquer J, Safont MJ, Balaña C, Sanchez-Cespedes M, García-Villanueva M, Arribas L, Esteller M: CpG island hypermethylation of the DNA repair enzyme methyltransferase predicts response to temozolomide in primary gliomas. Clin Cancer Res 10:4933-4938, 2004.
40. Pegg AE, Dolan ME, Moschel RC: Structure, function, and inhibition of O6-alkylguanine-DNA alkyltransferase. Prog Nucleic Acid Res Mol Biol 51:167-223, 1995.
41. Pieper RO, Patel S, Ting SA, Futscher BW, Costello JF: Methylation of CpG island transcription factor binding sites is unnecessary for aberrant silencing of the human MGMT gene. J Biol Chem 271:13916-13924, 1996.
42. Preusser M, Charles Janzer R, Felsberg J, Reifenberger G, Hamou MF, Diserens AC, Stupp R, Gorlia T, Marosi C, Heinzl H, Hainfellner JA, Hegi M: 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, 2008.
43. Qian XC, Brent TP: Methylation hot spots in the 5-flanking region denote silencing of the O6-methylguanine-DNA methyltransferase gene. Cancer Res 57:3672-3677, 1997.
44. Rood BR, Zhang H, Cogen PH: Intercellular heterogeneity of expression of the MGMT DNA repair gene in pediatric medulloblastoma. Neuro Oncol 6:200-207, 2004.
45. Sasai K, Nodagashira M, Nishihara H, Aoyanagi E, Wang L, Katoh M, Murata J, Ozaki Y, Ito T, Fujimoto S, Kaneko S, Nagashima K, Tanaka S: Careful exclusion of non-neoplastic brain components is required for an appropriate evaluation of O6-methylguanine-DNA methyltransferase status in glioma relationship between immunohistochemistry and methylation analysis. Am J Surg Pathol 32:1220-1227, 2008.
46. Stewart LA. Chemotherapy in adult high-grade glioma: A systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 359:1011-1018, 2002.
47. Watts GS, Pieper RO, Costello JF, Peng YM, Dalton WS, Futscher BW: Methylation of discrete regions of the O6-methylguanine DNA methyltransferase (MGMT) CpG island is associated with heterochromatinization of the MGMT transcription start site and silencing of the gene. Mol Cell Biol 17:5612-5619, 1997.