O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: Systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction

BMC Cancer

Volumn 11, Issue , 2011, Pages

  Brell, Marta ^a   Ibáñez, Javier ^a   Tortosa, Avelina ^b  

^a HOSPITAL UNIVERSITARIO SON ESPASES   (Spain)

^b UNIVERSITY OF BARCELONA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE;

AREA UNDER THE CURVE; ARTICLE; BRAIN METASTASIS; BRAIN TUMOR; COHORT ANALYSIS; DIAGNOSTIC ACCURACY; DIAGNOSTIC TEST ACCURACY STUDY; GLIOMA; HUMAN; IMMUNOHISTOCHEMISTRY; MAJOR CLINICAL STUDY; META ANALYSIS; METHODOLOGY; POLYMERASE CHAIN REACTION; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN METHYLATION; QUALITATIVE ANALYSIS; RECEIVER OPERATING CHARACTERISTIC; SENSITIVITY AND SPECIFICITY; SYSTEMATIC REVIEW; DNA METHYLATION; GENETICS; METABOLISM; NEOPLASM; PATHOLOGY; PROGNOSIS; REVIEW;

BRAIN NEOPLASMS; DNA METHYLATION; HUMANS; IMMUNOHISTOCHEMISTRY; NEOPLASMS; O(6)-METHYLGUANINE-DNA METHYLTRANSFERASE; POLYMERASE CHAIN REACTION; PROGNOSIS; PROMOTER REGIONS, GENETIC;

EID: 79251577095     PISSN: None     EISSN: 14712407     Source Type: Journal    
DOI: 10.1186/1471-2407-11-35     Document Type: Article

References (139)

1. 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 2002, 86:1888-1892. 10.1038/sj.bjc.6600372, 2375420, 12085181.
2. 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 1999, 59:793-797.
3. 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 1998, 16:3310-3315.
4. Gerson SL. Clinical relevance of MGMT in the treatment of cancer. J Clin Oncol 2002, 20:2388-2399. 10.1200/JCO.2002.06.110, 11981013.
5. Jones PA, Laird PW. Cancer epigenetics comes from age. Nat Genet 1999, 21:163-167. 10.1038/5947, 9988266.
6. Robertson KD, Jones PA. DNA methylation: past, present and furture directions. Carcinogenesis 2000, 21:461-467. 10.1093/carcin/21.3.461, 10688866.
7. Baylin SB, Herman JG. DNA hypermethylation in tumorigenesis: epigenetic joins genetics. Trends Genet 2000, 16:168-173. 10.1016/S0168-9525(99)01971-X, 10729832.
8. Esteller M, García-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 Eng J Med 2000, 343:1350-1354.
9. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JEC, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from Temozolamide in glioblastoma. N Engl J Med 2005, 352:997-1003. 10.1056/NEJMoa043331, 15758010.
10. Hegi ME, Diserens AC, Godard S, Dietrich PY, Regli L, Ostermann S, Otten P, Van Melle G, de Tribolet N, Strupp R. Clinical trial substantiates the predictive value of O6-Metylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with Temozolamide. Clin Cancer Res 2004, 10:1871-1874. 10.1158/1078-0432.CCR-03-0384, 15041700.
11. 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 2007, 83:173-179.
12. Everhard S, Kaloshi G, Crinière E, Benouaich-Amiel A, Lejeune J, Marie Y, Sanson M, Kujas M, Mokhtari K, Hoang-Xuan K, Delattre JY, Thillet J. MGMT Methylation: a marker of response to Temozolamide in low-grade gliomas. Ann Neurol 2006, 60:740-743. 10.1002/ana.21044, 17192931.
13. Kamiryo T, Tada K, Shiraishi S, Shinojima N, Kochi M, Ushio Y. 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 2004, 52:349-357.
14. Watanabe T, Katayama Y, Komine C, Yoshino A, Ogino A, Ohta T, Fukushima T. O6-Methylguanine-DNA methyltransferase methylation and TP53 mutation in malignant astrocytomas and their relationships with clinical course. Int J Cancer 2005, 113:581-587. 10.1002/ijc.20625, 15455376.
15. 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. Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. Lancet Oncol 2008, 9:29-38. 10.1016/S1470-2045(07)70384-4, 18082451.
16. Sadones J, Michotte A, Veld P, Chaskis C, Sciot R, Menten J, Joossens EJ, Strauven T, D'Hondt LA, Sartenaer D, Califice SF, Bierau K, Svensson C, De Greve J, Neyns B. MGMT promoter hypermethylation correlates with a survival benefit from temozolomide in patients with recurrent anaplastic astrocytoma but not glioblastoma. Eur J Cancer 2009, 45:146-153. 10.1016/j.ejca.2008.09.002, 18945611.
17. Shaw RJ, Hall GL, Lowe D, Liloglou T, Field JK, Sloan P, Risk JM. The role of pyrosequencing in head and neck cancer epigenetics: correlation of quantitative methylation data with gene expression. Arch Otolaryngol Head Neck Surg 2008, 134:251-256. 10.1001/archoto.2007.50, 18347248.
18. Preusser M, Elezi L, Hainfellner JA. Reliability and reproducibility of PCR-based testing of O6-methylguanine-DNA methyltransferase gene (MGMT) promoter methylation status in formalin-fixed and paraffin-embedded neurosurgical biopsy specimens. Clin Neuropathol 2008, 27:388-390.
19. Yip S, Iafrate AJ, Louis DN. Molecular diagnostic testing in malignant gliomas: a practical update on predictive markers. J Neuropathol Exp Neurol 2008, 67:1-15. 10.1097/nen.0b013e31815f65fb, 18091559.
20. Preusser M, Charles JR, 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 2008, 18:520-532.
21. Andersson U, Malmer B, Bergenheim AT, Brännström T, Henriksson R. Heterogeneity in the expression of markers for drug resistance in brain tumors. Clin Neuropathol 2004, 23:21-27.
22. Capper D, Mittelbronn M, Meyermann R, Schittenhelm J. Pitfalls in the assessment of MGMT expression and its correlation with survival in diffuse astrocytomas: proposal of feasible immunohistochemical approach. Acta Neuropathol 2008, 115:249-259. 10.1007/s00401-007-0310-x, 17965865.
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. Correlation between O6-methylguanine-DNA methyltransferase and survival in inoperable newly diagnosed glioblastoma patients treated with neoadjuvant temozolomide. J Clin Oncol 2007, 25:1470-1475. 10.1200/JCO.2006.07.4807, 17442989.
24. 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-alkyguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma. J Clin Oncol 1998, 16:3851-3857.
25. Idbaih A, Omuro A, Ducray F, Hoang-Xuan K. Molecular genetic markers as predictors of response to chemotherapy in gliomas. Curr Opin Oncol 2007, 19:606-611. 10.1097/CCO.0b013e3282f075f3, 17906460.
26. Jeuken JW, Cornelissen SJ, Vriezen M, Dekkers MM, Errami A, Sijben A, Boots-Sprenger SH, Wesseling P. MS-MLPA: an attractive alternative laboratory assay for robust, reliable, and semiquantitative detection of MGMT promoter hypermethylation in gliomas. Lab Invest 2007, 87:1055-1065. 10.1038/labinvest.3700664, 17700563.
27. McLendon RE, Cleveland L, Pegram C, Bigner SH, Bigner DD, Friedman HS. Immunohistochemical detection of the DNA repair enzyme O6-methylguanine-DNA methyltransferase in formalin-fixed, paraffin-embedded astrocytomas. Lab Invest 1998, 78:643-644.
28. Pollack IF, Hamilton RL, Sobol RW, Burnham J, Yates AJ, Holmes EJ, Zhou T, Finlay JL. O6-methylguanine-DNA methyltransferase expression strongly correlates with outcome in childhood malignant gliomas: results from the CCG-945 Cohort. J Clin Oncol 2006, 24:3431-3437. 10.1200/JCO.2006.05.7265, 16849758.
29. Rodriguez FJ, Thibodeau SN, Jenkins RB, Schowalter KV, Caron BL, O'Neil BP, James CD, Passe S, Slezak J, Giannini C. MGMT Immunohistochemical expression and promoter methylation in human glioblastoma. Appl Immunohistochem Mol Morphol 2008, 16:59-65.
30. Yachi K, Watanabe T, Ohta T, Fukushima T, Yoshino A, Ogino A, Katayama Y, Nagase H. Relevance of MSP assay for the detection of MGMT promoter hypermethylation in glioblastomas. Int J Oncol 2008, 33:469-475.
31. Brell M, Tortosa A, Verger E, Gil JM, Viñolas N, Villà S, Acebes JJ, Caral Pons JJ, Pujol T, Ferrer I, Ribalta T, Graus F. Prognostic significance of O6 - Methilguanine DNA methyltransferase determined by promoter methylation and immunohistochemical expression in anaplastic gliomas. Clin Cancer Res 2005, 11:5167-5171. 10.1158/1078-0432.CCR-05-0230, 16033832.
32. Ingold B, Schraml P, Heppner FL, Moch H. Homogeneous MGMT immunoreactivity correlates with an unmethylated MGMT promoter status in brain metastases of various solid tumors. PLoS ONE 2009, 4:e4775. 10.1371/journal.pone.0004775, 2652028, 19274096.
33. Preusser M. MGMT analysis at DNA, RNA and protein levels in glioblastoma tissue. Histol Histopathol 2009, 24:511-518.
34. Leeflang MM, Deeks JJ, Gatsonis C, Bossuyt PM. Systematic reviews of diagnostic test accuracy. Ann Intern Med 2008, 149:889-897. 2956514, 19075208.
35. Irwig L, Tosteson AN, Gatsonis C, Lau J, Colditz G, Chalmers TC, Mosteller F. Guidelines for meta-analyses evaluating diagnostic tests. Ann Intern Med 1994, 120:667-676.
36. Deville WL, Buntinx F, Bouter LM, Montori VM, de Vet HC, van der Windt DA, bezemer PD. Conducting systematic reviews of diagnostic studies: didactic guidelines. BMC Med Res Methodol 2002, 2:9. 10.1186/1471-2288-2-9, 117243, 12097142.
37. Virgili G, Conti AA, Murro V, Gensini GF, Gusinu R. Systematic reviews of diagnostic test accuracy and the Cochrane collaboration. Intern Emerg Med 2009, 4:255-258. 10.1007/s11739-009-0243-6, 19357825.
38. Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 2003, 3:25. 10.1186/1471-2288-3-25, 305345, 14606960.
39. Berman NG, Parker RA. Meta-analysis: neither quick nor easy. BMC Med Res Methodol 2002, 2:10. 10.1186/1471-2288-2-10, 122061, 12171604.
40. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC. Towards complete and accurate reporting of studies of diagnostic accuracy: The STARD Initiative. Ann Intern Med 2003, 138:40-44.
41. Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PM. The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol 2003, 56:1129-1135. 10.1016/S0895-4356(03)00177-X, 14615004.
42. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003, 327:557-560. 10.1136/bmj.327.7414.557, 192859, 12958120.
43. Sterne JA, Egger M. Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol 2001, 54:1046-1055. 10.1016/S0895-4356(01)00377-8, 11576817.
44. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997, 315:629-634. 2127453, 9310563.
45. Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A. Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol 2006, 6:31. 10.1186/1471-2288-6-31, 1552081, 16836745.
46. 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 C. Prognostic value of O(6)-methylguanine-DNA methyltransferase status in glioblastoma patients, assessed by five different methods. J Neurooncol 2010, 97:311-322. 10.1007/s11060-009-0031-1, 19841865.
47. Rood BR, Zhang H, Cogen PH. Intercellular heterogeneity of expression of the MGMT DNA repair gene in pediatric medulloblastoma. Neuro-Oncology 2004, 6:200-207. 10.1215/S1152851703000565, 1872000, 15279712.
48. Zhang D, Bai Y, Wang Y, Luo J, Ge Q, Qiao Y, Jia C, Lu Z. Detailed methylation patterns and protein expression profiles of MGMT in colorectal carcinoma surgical margins. Clin Biochem 2008, 41:19-25. 10.1016/j.clinbiochem.2007.09.010, 18028895.
49. Voelter V, Diserens AC, Moulin A, Nagel G, Yan P, Migliavacca E, Rimoldi D, Hamou MF, Kaina B, Leyvraz S, Hegi ME. Infrequent promoter methylation of the MGMT gene in liver metastases from uveal melanoma. Int J Cancer 2008, 123:1215-1218. 10.1002/ijc.23632, 18546261.
50. Martin P, Garcia-Cosio M, Santon A, Bellas C. Aberrant gene promoter methylation in plasma cell dyscrasias. Exp Mol Pathol 2008, 84:256-261. 10.1016/j.yexmp.2008.02.003, 18410922.
51. Rietschel P, Wolchok JD, Krown S, Gerst S, Jungbluth AA, Busam K, Smith K, Orlow I, Panageas K, Chapman PB. Phase II study of extended-dose temozolomide in patients with melanoma. J Clin Oncol 2008, 26:2299-2304. 10.1200/JCO.2007.14.5292, 18467721.
52. Lin Z, Gao M, Zhang X, Kim YS, Lee ES, Kim HK, Kim I. The hypermethylation and protein expression of p16 INK4A and DNA repair gene O6-methylguanine-DNA methyltransferase in various uterine cervical lesions. J Cancer Res Clin Oncol 2005, 131:364-370. 10.1007/s00432-004-0657-5, 15785933.
53. Furonaka O, Takeshima Y, Awaya H, Kushitani K, Kohno N, Inai K. Aberrant methylation and loss of expression of O6-Methylguanine-DNA methyltransferase in pulmonary squamous cell carcinoma and adenocarcinoma. Pathol Int 2005, 55:303-309. 10.1111/j.1440-1827.2005.01830.x, 15943786.
54. Brock MV, Gou M, Akiyama Y, Muller A, Wu TT, Montgomery E, Deasel M, Germonpré P, Rubinson L, Heitmiller RH, Yang SC, Forastiere AA, Baylin SB, Herman JG. Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma. Clin Cancer Res 2003, 9:2912-2919.
55. Nagasaka T, Sharp GB, Notohara K, Kambara T, Sasamoto H, Isozaki H, MacPhee DG, Jass JR, Tanaka N, Matsubara N. Hypermethylation of O6-Methylguanine-DNA methyltransefarse promoter may predict nonrecurrence after chemotherapy in colorectal cancer cases. Clin Cancer Res 2003, 9:5306-5312.
56. Zhang L, Lu W, Miao X, Xing D, Tan W, Lin D. Inactivation of DNA repair gene O6-Methylguanine-DNA methyltransferase by promoter hypermethylation and its relation to p53 mutations in esophageal squamous cell carcinoma. Carcinogenesis 2003, 24:1039-1044. 10.1093/carcin/bgg062, 12807758.
57. Matsukura S, Soejima H, Nakagawachi T, Yakushiji H, Ogawa A, Fukuhara M, Miyazaki K, Nakabeppu Y, Sekiguchi M, Mukai T. CpG methylation of MGMT and hMLH1 promoter in hepatocellular carcinoma associated with hepatitis viral infection. Br J Cancer 2003, 88:521-529. 10.1038/sj.bjc.6600743, 2377174, 12592365.
58. Mellai M, Caldera V, Annovazzi L, Chio A, Lanotte M, Cassoni P, Finocchiaro G, Schiffer D. MGMT promoter hypermethylation in a series of 104 glioblastomas. Cancer Genomics Proteomics 2009, 6:219-227.
59. Yang SH, Kim YH, Kim JW, Park CK, Park SH, Jung HW. Methylation status of the O6-Methylguanine-deoxyribonucleic acid methyltransferase gene promoter in World Health Organization grade III gliomas. J Korean Neurosurg Soc 2009, 46:385-388. 10.3340/jkns.2009.46.4.385, 2773399, 19893731.
60. Herfarth KK, Brent TP, Danam RP, Remack JS, Kodner IJ, Wells SA, Goodfellow PJ. A specific CpG methylation pattern of the MGMT promoter region associated with reduced MGMT expression in primary colorectal cancers. Mol Carcinog 1999, 24:90-98. 10.1002/(SICI)1098-2744(199902)24:2<90::AID-MC3>3.0.CO;2-B, 10078936.
61. Yin D, Xie D, Hofmann WK, Zhang W, Asotra K, Wong R, Black KL, Koeffler HP. DNA repair gene O6-methylguanine-DNA methyltransferase: promoter hypermethylation associated with decreased expression and G:C to A:T mutations of p53 in brain tumors. Mol Carcinog 2003, 36:23-31. 10.1002/mc.10094, 12503076.
62. Lazcoz P, Munoz J, Nistal M, Pestana A, Encio IJ, Castresana JS. Loss of heterozygosity and microsatellite instability on chromosome arm 10q in neuroblastoma. Cancer Genet Cytogenet 2007, 174:1-8. 10.1016/j.cancergencyto.2006.08.014, 17350460.
63. Qi J, Zhu YQ, Huang MF, Yang D. Hypermethylation of CpG island in O6-methylguanine-DNA methyltransferase gene was associated with K-ras G to A mutation in colorectal tumor. World J Gastroenterol 2005, 11:2022-2025.
64. Rimel BJ, Huettner P, Powell MA, Mutch DG, Goodfellow PJ. Absence of MGMT promoter methylation in endometrial cancer. Gynecol Oncol 2009, 112:224-228. 10.1016/j.ygyno.2008.08.038, 2949277, 18973931.
65. McCormack AI, McDonald KL, Gill AJ, Clark SJ, Burt MG, Campbell KA, Braund WJ, Little NS, Cook RJ, Grossman AB, Robinson BG, Clifton-Bligh RJ. Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and response to temozolomide in aggressive pituitary tumours. Clin Endocrinol (Oxf) 2009, 71:226-233. 10.1111/j.1365-2265.2008.03487.x, 19067722.
66. Nagasaka T, Goel A, Notohara K, Takahata T, Sasamoto H, Uchida T, Nishida N, Tanaka N, Boland CR, Matsubara N. Methylation pattern of the O6-methylguanine-DNA methyltransferase gene in colon during progressive colorectal tumorigenesis. Int J Cancer 2008, 122:2429-2436. 10.1002/ijc.23398, 2851179, 18240147.
67. Baumann S, Keller G, Puhringer F, Napieralski R, Feith M, Langer R, Hofler H, Stein HJ, Sarbia M. The prognostic impact of O6-Methylguanine-DNA Methyltransferase (MGMT) promotor hypermethylation in esophageal adenocarcinoma. Int J Cancer 2006, 119:264-268. 10.1002/ijc.21848, 16477636.
68. Maxwell JA, Johnson SP, Quinn A, McLendon RE, Ali-Osman F, Friedman AH, Herndon JE, Bierau K, Bigley J, Bigner DD, Friedman HS. Quantitative analysis of O6-alkylguanine-DNA alkyltransefarse in malignant glioma. Mol Cancer Ther 2006, 5:2531-2539. 10.1158/1535-7163.MCT-06-0106, 17041097.
69. Chu LC, Eberhart CG, Grossman SA, Herman JG. Epigenetic silencing of multiple genes in primary CNS lymphoma. Int J Cancer 2006, 119:2487-2491. 10.1002/ijc.22124, 16858686.
70. Uccella S, Cerutti R, Placidi C, Marchet S, Carnevali I, Bernasconi B, Proserpio I, Pinotti G, Tibiletti MG, Furlan D, Capella C. MGMT methylation in diffuse large B-cell lymphoma: validation of quantitative methylation-specific PCR and comparison with MGMT protein expression. J Clin Pathol 2009, 62:715-723. 10.1136/jcp.2009.064741, 19638543.
71. Möllemann M, Wolter M, Felsberg J, Collins VP, Reifenberger G. Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors. Int J Cancer 2005, 113:379-385.
72. Munot K, Bell SM, Lane S, Horgan K, Hanby AM, Speirs V. Pattern of expression of genes linked to epigenetic silencing in human breast cancer. Hum Pathol 2006, 37:989-999. 10.1016/j.humpath.2006.04.013, 16867861.
73. Wolf P, Hu YC, Doffek K, Sidransky D, Ahrendt SA. O(6)- Methylguanine-DNA methyltransferase promoter hypermethylation shifts the p53 mutational spectrum in non-small cell lung cancer. Cancer Res 2001, 61:8113-8117.
74. Lee GW, Kang JH, Kim IS, Kim HG, Ko GH, Lee JH, Kim DC, Song DH, Yang JW, Lee JS. Is inactivation of O(6)-methylguanine DNA methyltransferase still a favorable prognostic factor of patients with diffuse large B-cell lymphoma in the era of R-CHOP chemotherapy?. Leuk Lymphoma 2009, 50:1992-1998. 10.3109/10428190903312462, 19860620.
75. Herath NI, Walsh MD, Kew M, Smith JL, Jass JR, Young J, Leggett BA, Macdonald GA. Silencing of O6-methylguanine DNA methyltransferase in the absence of promoter hypermethylation in hepatocellular carcinomas from Australia and South Africa. Oncol Rep 2007, 17:817-822.
76. Lavon I, Zrihan D, Zelikovitch B, Fellig Y, Fuchs D, Soffer D, Siegal T. Longitudinal assessment of genetic and epigenetic markers in oligodendrogliomas. Clin Cancer Res 2007, 13:1429-1437. 10.1158/1078-0432.CCR-06-2050, 17332285.
77. Martin P, Santon A, Garcia-Cosio M, Bellas C. hMLH1 and MGMT inactivation as a mechanism of tumorigenesis in monoclonal gammopathies. Mod Pathol 2006, 19:914-921. 10.1038/modpathol.3800590, 16607377.
78. Ogawa T, Yoshida T, Tsuruta T, Saigenji K, Okayasu I. Genetic instability on chromosome 17 in the epithelium of non-polypoid colorectal carcinomas compared to polypoid lesions. Cancer Sci 2006, 97:1335-1342. 10.1111/j.1349-7006.2006.00334.x, 17032312.
79. Rossi D, Capello D, Gloghini A, Franceschetti S, Paulli M, Saglio G, Vitolo U, Pileri SA, Esteller M, Carbone A, Gaidano G. Aberrant promoter methylation of multiple genes throughout the clinico-pathologic spectrum of B-cell neoplasia. Haematologia 2004, 89:154-164.
80. Kim SH, Bae SI, Lee HS, Kim WH. Alteration of O6-methylguanie-DNA methyltransferase in colorectal neoplasms in sporadic and familial adenomatous polyposi patients. Mol Carcinog 2003, 37:32-38. 10.1002/mc.10116, 12720298.
81. Choy KW, Pang CP, To KF, Yu C, Ng JSK, Lam DSC. Impaired expression and promotor hypermethylation of O6-Methylguanine-DNA Methyltransferase in retinoblastoma tissues. Invest Ophthalmol Vis Sci (PA) 2002, 43:1344-1349.
82. Whitehall VL, Walsh MD, Young J, Leggett BA, Jass JR. Methylation of O6-methylguanine DNA methyltransferase characterizes a subset of colorectal cancer with low-level DNA microsatellite instability. Cancer Res 2001, 61:827-830.
83. Wu PF, Kuo KT, Kuo LT, Lin YT, Lee WC, Lu YS, Yang CH, Wu RM, Tu YK, Tasi JC, Tseng HM, Tseng SH, Cheng AL, Lin CH. O(6)- Methylguanine-DNA methyltransferase expression and prognostic value in brain metastases of lung cancers. Lung Cancer 2010, 68:484-490. 10.1016/j.lungcan.2009.08.010, 19740564.
84. Metellus P, Coulibaly B, Nanni I, Fina F, Eudes N, Giorgi R, Barrie M, Chinot O, Fuentes S, Dufour H, Ouafik L, Figarella-Branger D. Prognostic impact of O6-methylguanine-DNA methyltransferase silencing in patients with recurrent glioblastoma multiforme who undergo surgery and carmustine wafer implantation: a prospective patient cohort. Cancer 2009, 115:4783-4794. 10.1002/cncr.24546, 19637364.
85. Sonoda Y, Kumabe T, Watanabe M, Nakazato Y, Inoue T, Kanamori M, Tominaga T. Long-term survivors of glioblastoma: clinical features and molecular analysis. Acta Neurochir (Wien) 2009, 151:1349-1358. 10.1007/s00701-009-0387-1, 19730774.
86. Mikeska T, Bock C, El-Maarri O, Hubner A, Ehrentraut D, Schramm J, Felsberg J, Kahl P, Buttner R, Pietsch T, Waha A. Optimization of quantitative MGMT promoter methylation analysis using pyrosequencing and combined bisulfite restriction analysis. J Mol Diagn 2007, 9:368-381. 10.2353/jmoldx.2007.060167, 1899414, 17591937.
87. Parkinson JF, Wheeler HR, Clarkson A, Mckenkie CA, Biggs MT, Little NS, Cook RC, Messina M, Robinson BG, McDonald KL. Variation of O6-Methylguanine-DNA Methyltransferase (MGMT) promoter methylation in serial samples of glioblastoma. J Neurooncol 2008, 87:71-78. 10.1007/s11060-007-9486-0, 18004504.
88. 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 2004, 70:333-340. 10.1007/s11060-004-9170-6, 15662974.
89. Grasbon-Frodl EM, Kreth FW, Ruiter M, Schnell O, Bise K, Felsberg J, Reifenberg G, Tonn JC, Kretzschmar HA. Intratumoral homogeinity of MGMT promoter hypermetilation as demonstrated in serial stereotactic specimens for anaplastic astrocytomas and glioblastomas. Int J Cancer 2007, 121:2458-2464. 10.1002/ijc.23020, 17691113.
90. Everhard S, Tost J, El AH, Criniere E, Busato F, Marie Y, Gut IG, Sanson M, Mokhtari K, Laigle-Donadey F, Hoang-Xuan K, Delattre JY, Thillet J. Identification of regions correlating MGMT promoter methylation and gene expression in glioblastomas. Neuro Oncol 2009, 11:348-356. 10.1215/15228517-2009-001, 2743215, 19224763.
91. Kohonen-Corish MR, Daniel JJ, Chan C, Lin BP, Kwun SY, Dent OF, Dhillon VS, Trent RJ, Chapuis PH, Bokey EL. Low microsatellite instability is associated with poor prognosis in stage C colon cancer. J Clin Oncol 2005, 23:2318-2324. 10.1200/JCO.2005.00.109, 15800322.
92. Stupp R. Methylguanine methyltransefrase testing in glioblastoma: when and how?. J Clin Oncol 2007, 25:1459-1460. 10.1200/JCO.2006.09.7139, 17442986.
93. Shen L, Kondo Y, Rosner GL, Xiao L, Supunpong Hernandez N, Vilaythong J, Houlihan PS, Krouse RS, Prasad AR, Einspahr JG, Buckmeier J, Alberts DS, Hamilton SR, Issa J-PJ. MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst 2005, 97:1330-1338. 10.1093/jnci/dji275, 16174854.
94. Candiloro IL, Dobrovic A. Detection of MGMT promoter methylation in normal individuals is strongly associated with the T allele of the rs16906252 MGMT promoter single nucleotide polymorphism. Cancer Prev Res (Phila) 2009, 2:862-867. 10.1158/1940-6207.CAPR-09-0056, 19789298.
95. 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 2001, 92:2760-2768. 10.1002/1097-0142(20011201)92:11<2760::AID-CNCR10123>3.0.CO;2-8, 11753949.
96. Smith-Sorensen B, Lind GE, Skotheim RI, Fossa SD, Fodstad O, Stenwig A-E, Jakobsen KS, Lothe RA. Frequent promoter hypermethylation of the O6-Methylguanine-DNA methyltransferase (MGMT) gene in testicular cancer. Oncogene 2002, 21:8878-8884. 10.1038/sj.onc.1205978, 12483540.
97. Bhakat KK, Mitra S. CpG methylation-dependent repression of the human O6-Methylguanine-DNA methyltransferase gene linked to chromatin structure alteration. Carcinogenesis 2003, 24:1337-1345. 10.1093/carcin/bgg086, 12807730.
98. Esteller M, Corn PG, Baylin SB, Herman JG. A gene hypermethylation profile of human cancer. Cancer Res 2001, 61:3225-3229.
99. Lorente A, Mueller W, Urdangarin E, Lazcoz P, Lass U, von Deimling A, Castresana JS. RASSF1A, BLU, NORE1A, PTEN and MGMT expression and promoter methylation in gliomas and glioma cell lines and evidence of deregulated expression of de novo DNMTs. Brain Pathol 2009, 19:279-292. 10.1111/j.1750-3639.2008.00185.x, 18616639.
100. Baeza N, Weller M, Yonekawa Y, Kleihues P, Ohgaki H. PTEN methylation and expression in glioblastomas. Acta Neuropathol 2003, 106:479-485. 10.1007/s00401-003-0748-4, 12904991.
101. Iafrate AJ, Louis DN. "MGMT for pt mgmt": is Methylguanine-DNA Methyltransferase testing ready for patient management?. J Mol Diagn 2008, 10:308-310. 10.2353/jmoldx.2008.080043, 2438198, 18556768.
102. Fritz G, Tano K, Mitra S, Kaina B. Inducibility of the DNA repair gene encoding O6-methylguanine-DNA methyltransferase in mammalian cells by DNA-damaging treatments. Mol Cell Biol 1991, 11:4660-4668. 361355, 1875945.
103. Cahill DP, Levine KK, Betensky RA, Codd PJ, Romany CA, Reavie LB, Batchelor TT, Futreal PA, Stratton MR, Curry WT, Iafrate AJ, Louis DN. Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment. Clin Cancer Res 2007, 13:2038-2045. 10.1158/1078-0432.CCR-06-2149, 2873832, 17404084.
104. Christmann M, Nagel G, Horn S, Krahn U, Wiewrodt D, Sommer C, Kaina B. MGMT activity, promoter methylation and immunohistochemistry of pretreatment and recurrent malignant gliomas: a comparative study on astrocytoma and glioblastoma. Int J Cancer 2010, 127:2106-2118. 10.1002/ijc.25229, 20131314.
105. Eoli M, Menghi F, Bruzzone MG, De ST, Valletta L, Pollo B, Bissola L, Silvani A, Bianchessi D, D'Incerti L, Filippini G, Broggi G, Boiardi A, Finocchiaro G. 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 2007, 13:2606-2613. 10.1158/1078-0432.CCR-06-2184, 17473190.
106. Jung TY, Jung S, Moon KS, Kim IY, Kang SS, Kim YH, Park CS, Lee KH. Changes of the O6-methylguanine-DNA methyltransferase promoter methylation and MGMT protein expression after adjuvant treatment in glioblastoma. Oncol Rep 2010, 23:1269-1276. 10.3892/or_00000760, 20372840.
107. Nagane M, Kobayashi K, Ohnishi A, Shimizu S, Shiokawa Y. Prognostic significance of O6-methylguanine-DNA methyltransferase protein expression in patients with recurrent glioblastoma treated with temozolomide. Jpn J Clin Oncol 2007, 37:897-906. 10.1093/jjco/hym132, 18156172.
108. Wiewrodt D, Nagel G, Dreimuller N, Hundsberger T, Perneczky A, Kaina B. MGMT in primary and recurrent human glioblastomas after radiation and chemotherapy and comparison with p53 status and clinical outcome. Int J Cancer 2008, 122:1391-1399. 10.1002/ijc.23219, 18000822.
109. Brandes AA, Franceschi E, Tosoni A, Bartolini S, Bacci A, Agati R, Ghimenton C, Turazzi S, Talacchi A, Skrap M, Marucci G, Volpin L, Morandi L, Pizzolitto S, Gardiman M, Andreoli A, Calbucci F, Ermani M. O(6)-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications. Neuro Oncol 2010, 12:283-288.
110. Parkinson JF, Wheeler HT, McDonald KL. Contribution of DNA repair mechanisms to determining chemotherapy response in high-grade glioma. J Clin Neurosci 2008, 15:1-8. 10.1016/j.jocn.2007.06.005, 18037296.
111. Candiloro IL, Mikeska T, Hokland P, Dobrovic A. Rapid analysis of heterogeneously methylated DNA using digital methylation-sensitive high resolution melting: application to the CDKN2B (p15) gene. Epigenetics Chromatin 2008, 1:7. 10.1186/1756-8935-1-7, 2590600, 19014416.
112. Weller M, Stupp R, Reifenberger G, Brandes AA, van den Bent MJ, Wick W, Hegi ME. MGMT promoter methylation in malignant gliomas: ready for personalized medicine?. Nat Rev Neurol 2010, 6:39-51. 10.1038/nrneurol.2009.197, 19997073.
113. Anda T, Shabani HK, Tsunoda K, Tokunaga Y, Kaminogo M, Shitaba S, Hayashi T, Iseki M. Relationsip between expression of O6-methylguanine-DNA methyltransferase, glutathione-S-transferase π in glioblastoma and the survival of the patients treated with nimustine hydrochloride: An immunohistochemical analysis. Neurol Res 2003, 25:241-248. 10.1179/016164103101201445, 12739231.
114. Nakasu S, Fukami T, Jito J, Matsuda M. Prognostic significance of loss of O6-methylguanine-DNA methyltransferase expression in supratentorial diffuse low-grade astrocytoma. Surg Neurol 2007, 68:603-608. 10.1016/j.surneu.2006.12.053, 17825378.
115. Nakagawa T, Ido K, Sakuma T, Takeuchi H, Sato K, Kubota T. Prognostic significance of the immunohistochemical expression of O6-methylguanine-DNA methyltransferase, P-glycoprotein, and multidrug resistance protein-1 in glioblastomas. Neuropathology 2009, 29:388.
116. Cao VT, Jung TY, Jung S, Jin SG, Moon KS, Kim IY, Kang SS, Park CS, Lee KH, Chae HJ. The correlation and prognostic significance of MGMT promoter methylation and MGMT protein in glioblastomas. Neurosurgery 2009, 65:866-875. 10.1227/01.NEU.0000357325.90347.A1, 19834398.
117. Sonoda Y, Yokosawa M, Saito R, Kanamori M, Yamashita Y, Kumabe T, Watanabe M, Tominaga T. O(6)-Methylguanine DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression is correlated with progression-free survival in patients with glioblastoma. Int J Clin Oncol 2010, 15:352-358. 10.1007/s10147-010-0065-6, 20232102.
118. Kuo LT, Kuo KT, Lee MJ, Wei CC, Scaravilli F, Tsai JC, Tseng HM, Kuo MF, Tu YK. Correlation among pathology, genetic and epigenetic profiles, and clinical outcome in oligodendroglial tumors. Int J Cancer 2009, 124:2872-2879. 10.1002/ijc.24303, 19330828.
119. Felsberg J, Rapp M, Loeser S, Fimmers R, Stummer W, Goeppert M, Steiger HJ, Friedensdorf B, Reifenberger G, Sabel MC. Prognostic significance of molecular markers and extent of resection in primary glioblastoma patients. Clin Cancer Res 2009, 15:6683-6693. 10.1158/1078-0432.CCR-08-2801, 19861461.
120. Gerson SL. MGMT: its role in cancer aetiology and cancer therapeutics. Nat Rev Cancer 2004, 4:296-307. 10.1038/nrc1319, 15057289.
121. Esteller M, Herman JG. Generating mutations but providing chemosensitivity: the role of O6-Methylguanine DNA methyltransferase in human cancer. Oncogene 2004, 23:1-8. 10.1038/sj.onc.1207316, 14712205.
122. Herman JG, Baylin SB. Gene silencing in cancer is association with promoter hypermethylation. N Engl J Med 2003, 349:2042-2054. 10.1056/NEJMra023075, 14627790.
123. Deeks JJ. Systematic reviews in health care: Systematic reviews of evaluations of diagnostic and screening tests. BMJ 2001, 323:157-162. 10.1136/bmj.323.7305.157, 1120791, 11463691.
124. Leeflang MM, Debets-Ossenkopp YJ, Visser CE, Scholten RJ, Hooft L, Bijlmer HA, Reitsma JB, Bossuyt PM, Vandenbroucke-Grauls CM. Galactomannan detection for invasive aspergillosis in immunocompromised patients. Cochrane Database Syst Rev 2008, CD007394.
125. Sasai K, Nodagashira M, 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 appropiate evaluation of O6-methylguanine-DAN methyltransferase status in glioma. Am J Surg Pathol 2008, 32:1220-1227. 10.1097/PAS.0b013e318164c3f0, 18580490.
126. Buccoliero AM, Castiglione F, Rossi Deglínnocenti D, Paglierani M, Maio V, Gheri CF, Garbini F, Moncini D, Taddei A, Sardi I, Sanzo M, Giordano F, Mussa F, Genitori L, Taddei GL. O6-Methylguanine-DNA-Methylytansefrase in recurring anaplastic ependymomas: PCR and immunohistochemistry. J Chemother 2008, 20:263-268.
127. Cankovic M, Mikkelsen T, Rosenblum ML, Zarbo RJ. A simplified laboratory validated assay for MGMT promoter hypermethylation analysis of glioma specimens from formalin-fixed paraffin-embedded tissue. Lab Invest 2007, 87:392-397.
128. Kim JI, Suh JT, Choi KU, Kang HJ, Shin DH, Lee IS, Moon TY, Kim WT. Inactivation of O(6)-methylguanine-DNA methyltransferase in soft tissue sarcomas: association with K-ras mutations. Hum Pathol 2009, 40:934-941. 10.1016/j.humpath.2009.01.005, 19356788.
129. Zou XP, Zhang B, Zhang XQ, Chen M, Cao J, Liu WJ. Promoter hypermethylation of multiple genes in early gastric adenocarcinoma and precancerous lesions. Hum Pathol 2009, 40:1534-1542. 10.1016/j.humpath.2009.01.029, 19695681.
130. Kuester D, El-Rifai W, Peng D, Ruemmele P, Kroeckel I, Peters B, Moskaluk CA, Stolte M, Monkemuller K, Meyer F, Schulz HU, Hartmann A, Roessner A, Schneider-Stock R. Silencing of MGMT expression by promoter hypermethylation in the metaplasia-dysplasia-carcinoma sequence of Barrett's esophagus. Cancer Lett 2009, 275:117-126. 10.1016/j.canlet.2008.10.009, 19027227.
131. Mikami T, Yoshida T, Numata Y, Shiraishi H, Araki K, Guiot MC, Jass JR, Okayasu I. Low frequency of promoter methylation of O6-methylguanine DNA methyltransferase and hMLH1 in ulcerative colitis-associated tumors: comparison with sporadic colonic tumors. Am J Clin Pathol 2007, 127:366-373. 10.1309/RFETXN6387KLQ1LD, 17276933.
132. Kawaguchi K, Oda Y, Saito T, Yamamoto H, Takahira T, Kobayashi C, Tamiya S, Tateishi N, Iwamoto Y, Tsuneyoshi M. DNA hypermethylation status of multiple genes in soft tissue sarcomas. Mod Pathol 2006, 19:106-114. 10.1038/modpathol.3800502, 16258501.
133. Fox EJ, Leahy DT, Geraghty R, Mulcahy HE, Fennelly D, Hyland JM, O'Donoghue DP, Sheahan K. Mutually exclusive promoter hypermethylation patterns of hMLH1 and O6-methylguanine DNA methyltransferase in colorectal cancer. J Mol Diagn 2006, 8:68-75. 10.2353/jmoldx.2006.050084, 1867561, 16436636.
134. Shen L, Kondo Y, Rosner GL, Xiao L, Supunpong Hernandez N, Vilaythong J, Houlihan PS, Krouse RS, Prasad AR, Einspahr JG, Buckmeier J, Alberts DS, Hamilton SR, Issa J-PJ. MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst 2005, 97:1330-1338. 10.1093/jnci/dji275, 16174854.
135. Koga Y, Kitajima Y, Miyoshi A, Sato K, Kitahara K, Soejima H, Miyazaki L. Tumor progression through epigenetic gene silencing of O(6)-methylguanine-DNA methyltransferase in human biliary tract cancers. Ann Surg Oncol 2005, 12:354-363. 10.1245/ASO.2005.07.020, 15915369.
136. Kang GH, Lee S, Lee HJ, Hwang KS. Aberrant CpG island hypermethylation of multiple genes in prostate cancer and prostatic intraepithelial neoplasia. J Pathol 2004, 202:233-240. 10.1002/path.1503, 14743506.
137. Zhang YJ, Chen Y, Ahsan H, Lunn RM, Lee PH, Chen CJ, Santella RM. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation and its relationship to aflatoxin B1-DNA adducts and p53 mutation in hepatocellular carcinoma. Int J Cancer 2003, 103:440-444. 10.1002/ijc.10852, 12478658.
138. Esteller M, Gaidano G, Goodman SN, Zagonel V, Capello D, Botto B, Rossi D, Gloghini A, Vitolo U, Carbone A, Baylin SB, Herman JG. Hypermethylation of the DNA repair gene O(6)-methylguanine DNA methyltransferase and survival of patients with diffuse large B-cell lymphoma. J Natl Cancer Inst 2002, 94:26-32.
139. Hayashi H, Yazawa T, Okudela K, Nagai J, Ito T, Kanisawa M, Kitamura H. Inactivation of O6-Methylguanine-DNA Methyltransferase in human lung adenocarcinoma relates to high-grade histology and worse prognosis among smokers. Jpn J Cancer Res 2002, 93:184-189.