The combination of IDH1 mutations and MGMT methylation status predicts survival in glioblastoma better than either IDH1 or MGMT alone

Neuro-Oncology

Volumn 16, Issue 9, 2014, Pages 1263-1273

  Molenaar, Remco J ^a   Verbaan, Dagmar ^b   Lamba, Simona ^c   Zanon, Carlo ^c   Jeuken, Judith W M ^d,i   Boots Sprenger, Sandra H E ^d   Wesseling, Pieter ^d,e   Hulsebos, Theo J M ^a   Troost, Dirk ^a   Van Tilborg, Angela A ^a,d   Leenstra, Sieger ^f,g   Vandertop, W Peter ^b,e   Bardelli, Alberto ^c,h   Van Noorden, Cornelis J F ^a   Bleeker, Fonnet E ^a,b,c  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

^b ACADEMIC MEDICAL CENTER   (Netherlands)

^c CANDIOLO CANCER INSTITUTE   (Italy)

^d RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^e VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^f CPRLab   (Netherlands)

^g ERASMUS MEDICAL CENTER   (Netherlands)

^h FIRC INSTITUTE OF MOLECULAR ONCOLOGY   (Italy)

ⁱ Stichting Laboratoria voor Pathologie en Medische Microbiologie   (Netherlands)

Author keywords

Genetic and epigenetic; Glioblastoma; IDH1; MGMT; Survival prediction

Indexed keywords

GENOMIC DNA; ISOCITRATE DEHYDROGENASE 1; METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE; DNA LIGASE; DNA METHYLTRANSFERASE; IDH1 PROTEIN, HUMAN; ISOCITRATE DEHYDROGENASE; MGMT PROTEIN, HUMAN; TUMOR SUPPRESSOR PROTEIN;

ADULT; AGED; ARTICLE; CANCER PATIENT; CANCER PROGNOSIS; CANCER RADIOTHERAPY; CANCER SURVIVAL; CANCER TISSUE; CONTROLLED STUDY; DNA METHYLATION; EPIGENETICS; FEMALE; GENE LOCUS; GENETIC ASSOCIATION; GENOTYPE; GLIOBLASTOMA; HUMAN; HUMAN TISSUE; KARNOFSKY PERFORMANCE STATUS; MAJOR CLINICAL STUDY; MALE; MULTIPLEX LIGATION DEPENDENT PROBE AMPLIFICATION; OVERALL SURVIVAL; POLYMERASE CHAIN REACTION; PREDICTIVE VALUE; PROGRESSION FREE SURVIVAL; PROMOTER REGION; RADIATION DOSE; SOMATIC MUTATION; SURVIVAL TIME; WILD TYPE; BRAIN TUMOR; GENETIC EPIGENESIS; GENETICS; MIDDLE AGED; MORTALITY; MUTATION; SURVIVAL; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; BRAIN NEOPLASMS; DNA METHYLATION; DNA MODIFICATION METHYLASES; DNA REPAIR ENZYMES; EPIGENESIS, GENETIC; FEMALE; GLIOBLASTOMA; HUMANS; ISOCITRATE DEHYDROGENASE; MALE; MIDDLE AGED; MUTATION; SURVIVAL ANALYSIS; TUMOR SUPPRESSOR PROTEINS;

EID: 84906505215     PISSN: 15228517     EISSN: 15235866     Source Type: Journal    
DOI: 10.1093/neuonc/nou005     Document Type: Article

References (75)

1. Stupp R, Hegi ME, Mason WP, et al. 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. 2009;10(5):459-466.
2. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-996. (Pubitemid 40349501)
3. Ohgaki H, Kleihues P. Genetic pathways to primary and secondary glioblastoma. Am J Pathol. 2007;170(5):1445-1453. (Pubitemid 47339290)
4. Bleeker FE, Molenaar RJ, Leenstra S. Recent advances in the molecular understanding of glioblastoma. J Neurooncol. 2012;108(1):11-27.
5. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997-1003. (Pubitemid 40349502)
6. Weller M, Felsberg J, Hartmann C, et al. Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network. J Clin Oncol. 2009;27(34):5743-5750.
7. Zawlik I, Vaccarella S, Kita D, et al. Promoter methylation and polymorphisms of the MGMT gene in glioblastomas: a population-based study. Neuroepidemiology. 2009;32(1):21-29.
8. Nagarajan RP, Costello JF. Epigenetic mechanisms in glioblastoma multiforme. Semin Cancer Biol. 2009;19(3):188-197.
9. Martinez R, Esteller M. The DNA methylome of glioblastoma multiforme. Neurobiol Dis. 2010;39(1):40-46.
10. Parsons DW, Jones S, Zhang X, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321(5897):1807-1812.
11. Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360(8):765-773.
12. Balss J, Meyer J, Mueller W, et al. Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol. 2008;116(6):597-602.
13. Bleeker FE, Lamba S, Leenstra S, et al. IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat. 2009;30(1):7-11.
14. Ichimura K, Pearson DM, Kocialkowski S, et al. IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas. Neuro Oncol. 2009;11(4):341-347.
15. Nobusawa S, Watanabe T, Kleihues P, et al. IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res. 2009;15(19):6002-6007.
16. +-dependent IDH activity in glioblastoma. Acta Neuropathol. 2010;119(4):487-494.
17. Sanson M, Marie Y, Paris S, et al. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol. 2009;27(25):4150-4154.
18. Gravendeel LA, Kouwenhoven MC, Gevaert O, et al. Intrinsic gene expression profiles of gliomas are a better predictor of survival than histology. Cancer Res. 2009;69(23):9065-9072.
19. Phillips HS, Kharbanda S, Chen R, et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell. 2006;9(3):157-173. (Pubitemid 43357943)
20. Verhaak RG, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17(1):98-110.
21. Bleeker FE, Lamba S, Zanon C, et al. Absence of AKT1 mutations in glioblastoma. PLoS One. 2009;4(5):e5638.
22. TCGAN. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455(7216):1061-1068.
23. Schouten JP, McElgunn CJ, Waaijer R, et al. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res. 2002;30(12):e57.
24. Jeuken J, Sijben A, Alenda C, et al. Robust detection of EGFR copy number changes and EGFR variant III: technical aspects and relevance for glioma diagnostics. Brain Pathol. 2009;19(4):661-671.
25. Jeuken J, Cornelissen S, Boots-Sprenger S, et al. Multiplex ligation-dependent probe amplification: a diagnostic tool for simultaneous identification of different genetic markers in glial tumors. J Mol Diagn. 2006;8(4):433-443. (Pubitemid 44377925)
26. Jeuken JW, Cornelissen SJ, Vriezen M, et al. MS-MLPA: an attractive alternative laboratory assay for robust, reliable, and semiquantitative detection of MGMT promoter hypermethylation in gliomas. Lab Invest. 2007;87(10):1055-1065. (Pubitemid 47429190)
27. Boots-Sprenger SH, Sijben A, Rijntjes J, et al. Significance of complete 1p/19q co-deletion, IDH1 mutation and MGMT promoter methylation in gliomas: use with caution. Mod Pathol. 2013;26(7):922-929.
28. Mulholland S, Pearson DM, Hamoudi RA, et al. MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations. Int J Cancer. 2012;131(5):1104-1113.
29. Gravendeel LA, Kloosterhof NK, Bralten LB, et al. Segregation of non-p.R132H mutations in IDH1 in distinct molecular subtypes of glioma. Hum Mutat. 2010;31(3):E1186-E1199.
30. French PJ, Swagemakers SM, Nagel JH, et al. Gene expression profiles associated with treatment response in oligodendrogliomas. Cancer Res. 2005;65(24):11335-11344. (Pubitemid 41821690)
31. Krex D, Klink B, Hartmann C, et al. Long-term survival with glioblastoma multiforme. Brain. 2007;130(Pt 10):2596-2606. (Pubitemid 47511715)
32. SongTao Q, Lei Y, Si G, et al. IDH mutations predict longer survival and response to temozolomide in secondary glioblastoma. Cancer Sci. 2012;103(2):269-273.
33. Burton EC, Lamborn KR, Feuerstein BG, et al. Genetic aberrations defined by comparative genomic hybridization distinguish long-term from typical survivors of glioblastoma. Cancer Res. 2002;62(21):6205-6210. (Pubitemid 35244472)
34. Nakamura M, Yang F, Fujisawa H, et al. Loss of heterozygosity on chromosome 19 in secondary glioblastomas. J Neuropathol Exp Neurol. 2000;59(6):539-543. (Pubitemid 30368313)
35. Institute WTS. Catalogue Of Somatic Mutations In Cancer (COSMIC).
36. Ohgaki H, Dessen P, Jourde B, et al. Genetic pathways to glioblastoma: a population-based study. Cancer Res. 2004;64(19):6892-6899. (Pubitemid 39330996)
37. Eoli M, Menghi F, Bruzzone MG, et al. 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(9):2606-2613. (Pubitemid 46788026)
38. Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res. 2013;19(4):764-772.
39. Lu C, Ward PS, Kapoor GS, et al. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature. 2012;483(7390):474-478.
40. Turcan S, Rohle D, Goenka A, et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature. 2012;483(7390):479-483.
41. Fietkau R, Putz F, Lahmer G, et al. Can MGMT promoter methylation status be used as a prognostic and predictive marker for glioblastoma multiforme at the present time?: A word of caution. Strahlenther Onkol. 2013;189(12):993-995.
42. Lee JC, Vivanco I, Beroukhim R, et al. Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain. PLoS Med. 2006;3(12):e485.
43. Hartmann C, Hentschel B, Wick W, et al. Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. Acta Neuropathol. 2010;120(6):707-718.
44. Juratli TA, Kirsch M, Geiger K, et al. The prognostic value of IDH mutations and MGMT promoter status in secondary high-grade gliomas. J Neurooncol. 2012;110(3):325-333.
45. Carrillo JA, Lai A, Nghiemphu PL, et al. Relationship between tumor enhancement, edema, IDH1 mutational status, MGMT promoter methylation, and survival in glioblastoma. Am J Neuroradiol. 2012;33(7):1349-1355.
46. Leibel SA, Sheline GE. Radiation therapy for neoplasms of the brain. J Neurosurg. 1987;66(1):1-22. (Pubitemid 17214276)
47. Walker MD, Strike TA, Sheline GE. An analysis of dose-effect relationship in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys. 1979;5(10):1725-1731. (Pubitemid 10187518)
48. Zinn PO, Colen RR, Kasper EM, et al. Extent of resection and radiotherapy in GBM: A 1973 to 2007 surveillance, epidemiology and end results analysis of 21,783 patients. Int J Oncol. 2013;42(3):929-934.
49. Chaudhry NS, Shah AH, Ferraro N, et al. Predictors of long-term survival in patients with glioblastoma multiforme: advancements from the last quarter century. Cancer Invest. 2013;31(5):287-308.
50. Bloch O, Han SJ, Cha S, et al. Impact of extent of resection for recurrent glioblastoma on overall survival: clinical article. J Neurosurg. 2012;117(6):1032-1038.
51. Kuhnt D, Becker A, Ganslandt O, et al. Correlation of the extent of tumor volume resection and patient survival in surgery of glioblastoma multiforme with high-field intraoperative MRI guidance. Neuro Oncol. 2011;13(12):1339-1348.
52. Ewelt C, Goeppert M, Rapp M, et al. Glioblastoma multiforme of the elderly: the prognostic effect of resection on survival. J Neurooncol. 2011;103(3):611-618.
53. Wang Y, Chen X, Zhang Z, et al. Comparison of the clinical efficacy of temozolomide (TMZ) versus nimustine (ACNU)-based chemotherapy in newly diagnosed glioblastoma. Neurosurg Rev. 2014;37(1):73-78.
54. Scoccianti S, Magrini SM, Ricardi U, et al. Patterns of care and survival in a retrospective analysis of 1059 patients with glioblastoma multiforme treated between 2002 and 2007: a multicenter study by the Central Nervous System Study Group of Airo (italian Association of Radiation Oncology). Neurosurgery. 2010;67(2):446-458.
55. Lee Y, Scheck AC, Cloughesy TF, et al. Gene expression analysis of glioblastomas identifies the major molecular basis for the prognostic benefit of younger age. BMC Med Genomics. 2008;1:52.
56. Noushmehr H, Weisenberger DJ, Diefes K, et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010;17(5):510-522.
57. van den Bent MJ, Gravendeel LA, Gorlia T, et al. A hypermethylated phenotype is a better predictor of survival than MGMT methylation in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951. Clin Cancer Res. 2011;17(22):7148-7155.
58. Toedt G, Barbus S, Wolter M, et al. Molecular signatures classify astrocytic gliomas by IDH1 mutation status. Int J Cancer. 2011;128(5):1095-1103.
59. Watanabe T, Nobusawa S, Kleihues P, et al. IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol. 2009;174(4):1149-1153.
60. Kanamori M, Kumabe T, Shibahara I, et al. Clinical and histological characteristics of recurrent oligodendroglial tumors: comparison between primary and recurrent tumors in 18 cases. Brain Tumor Pathol. 2013;30(3):151-159.
61. Kim JH, Bae Kim Y, Han JH, et al. Pathologic diagnosis of recurrent glioblastoma: morphologic, immunohistochemical, and molecular analysis of 20 paired cases. Am J Surg Pathol. 2012;36(4):620-628.
62. Felsberg J, Thon N, Eigenbrod S, et al. Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas. Int J Cancer. 2011;129(3):659-670.
63. Wick W, Meisner C, Hentschel B, et al. Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation. Neurology. 2013;81(17):1515-1522.
64. Frenel JS, Leux C, Loussouarn D, et al. Combining two biomarkers, IDH1/2 mutations and 1p/19q codeletion, to stratify anaplastic oligodendroglioma in three groups: a single-center experience. J Neurooncol. 2013;114(1):85-91.
65. Mur P, Mollejo M, Ruano Y, et al. Codeletion of 1p and 19q determines distinct gene methylation and expression profiles in IDH-mutated oligodendroglial tumors. Acta Neuropathol. 2013;126(2):277-289.
66. Leu S, von Felten S, Frank S, et al. IDH/MGMT-driven molecular classification of low-grade glioma is a strong predictor for long-term survival. Neuro Oncol. 2013;15(4):469-479.
67. Leibetseder A, Ackerl M, Flechl B, et al. Outcome and molecular characteristics of adolescent and young adult patients with newly diagnosed primary glioblastoma: a study of the Society of Austrian Neurooncology (SANO). Neuro Oncol. 2013;15(1):112-121.
68. Bady P, Sciuscio D, Diserens AC, et al. MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status. Acta Neuropathol. 2012;124(4):547-560.
69. Hartmann C, Meyer J, Balss J, et al. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol. 2009;118(4):469-474.
70. Wick W, Platten M, Meisner C, et al. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol. 2012;13(7):707-715.
71. Malmstrom A, Gronberg BH, Marosi C, et al. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol. 2012;13(9):916-926.
72. Motomura K, Natsume A, Kishida Y, et al. Benefits of interferon-B and temozolomide combination therapy for newly diagnosed primary glioblastoma with the unmethylated MGMT promoter: A multicenter study. Cancer. 2011;117(8):1721-1730.
73. ClinicalTrials.gov. http://www.clinicaltrials.gov/ct2/results?Term= MGMT+glioblastoma&Search=Search. Accessed June 18, 2013.
74. Rohle D, Popovici-Muller J, Palaskas N, et al. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science. 2013;340(6132):626-630.
75. Williams R. Cancer Growth Curtailed. The Scientist 2013; http://www.the-scientist.com/?Articles.view/articleNo/35002/title/ Cancer-Growth-Curtailed/. Accessed June 12, 2013.