MGMT as a potential stratification marker in relapsed high‐grade glioma of children: The HIT‐GBM experience

Studies in adults with malignant glioma suggest MGMT methylation as a stratification marker. Similar data for children are sparse. We investigated the impact of MGMT methylation and expression on survival of children with high‐grade glioma (HGG) registered into the German HIT‐GBM database receiving temozolomide (TMZ) as part of their treatment (n = 21 relapsed, n = 4 primary).

[1]  M. Weller,et al.  New (alternative) temozolomide regimens for the treatment of glioma. , 2009, Neuro-oncology.

[2]  H. Heinzl,et al.  Anti‐O6‐Methylguanine‐Methyltransferase (MGMT) Immunohistochemistry in Glioblastoma Multiforme: Observer Variability and Lack of Association with Patient Survival Impede Its Use as Clinical Biomarker * , 2008, Brain pathology.

[3]  J. Herman,et al.  Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  H. Mehdorn,et al.  A methylation-specific and SYBR-green-based quantitative polymerase chain reaction technique for O6-methylguanine DNA methyltransferase promoter methylation analysis. , 2008, Analytical biochemistry.

[5]  A. Brandes,et al.  MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  D. Capper,et al.  Pitfalls in the assessment of MGMT expression and in its correlation with survival in diffuse astrocytomas: proposal of a feasible immunohistochemical approach , 2008, Acta Neuropathologica.

[7]  C. Kramm,et al.  Subpopulations of malignant gliomas in pediatric patients: analysis of the HIT-GBM database , 2008, Journal of Neuro-Oncology.

[8]  B. O'neill,et al.  MGMT Immunohistochemical Expression and Promoter Methylation in Human Glioblastoma , 2007, Applied immunohistochemistry & molecular morphology : AIMM.

[9]  G. Reifenberger,et al.  Intratumoral homogeneity of MGMT promoter hypermethylation as demonstrated in serial stereotactic specimens from anaplastic astrocytomas and glioblastomas , 2007, International journal of cancer.

[10]  Gabriele Schackert,et al.  Long-term survival with glioblastoma multiforme. , 2007, Brain : a journal of neurology.

[11]  J. Schramm,et al.  Optimization of quantitative MGMT promoter methylation analysis using pyrosequencing and combined bisulfite restriction analysis. , 2007, The Journal of molecular diagnostics : JMD.

[12]  J. Herman,et al.  Frequent hypermethylation of the DNA repair gene MGMT in long-term survivors of glioblastoma multiforme , 2007, Journal of Neuro-Oncology.

[13]  A. Donson,et al.  MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma , 2007, Pediatric blood & cancer.

[14]  M. Frühwald,et al.  Frequent but borderline methylation of p16INK4a and TIMP3 in medulloblastoma and sPNET revealed by quantitative analyses , 2007, Journal of Neuro-Oncology.

[15]  K. Hoang-Xuan,et al.  MGMT methylation: A marker of response to temozolomide in low‐grade gliomas , 2006, Annals of neurology.

[16]  T. Zhou,et al.  O6-methylguanine-DNA methyltransferase expression strongly correlates with outcome in childhood malignant gliomas: results from the CCG-945 Cohort. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  N. Osada,et al.  Epigenetic repression of RASSF1A but not CASP8 in supratentorial PNET (sPNET) and atypical teratoid/rhabdoid tumors (AT/RT) of childhood , 2006, Oncogene.

[18]  I. Ferrer,et al.  Prognostic Significance of O6-Methylguanine-DNA Methyltransferase Determined by Promoter Hypermethylation and Immunohistochemical Expression in Anaplastic Gliomas , 2005, Clinical Cancer Research.

[19]  R. Ellenbogen,et al.  O6-Methylguanine-DNA Methyltransferase, O6-Benzylguanine, and Resistance to Clinical Alkylators in Pediatric Primary Brain Tumor Cell Lines , 2005, Clinical Cancer Research.

[20]  R. Mirimanoff,et al.  MGMT gene silencing and benefit from temozolomide in glioblastoma. , 2005, The New England journal of medicine.

[21]  M. Paz,et al.  CpG island hypermethylation of the DNA repair enzyme methyltransferase predicts response to temozolomide in primary gliomas. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[22]  L. Harris,et al.  Epigenetic regulation of O6-methylguanine-DNA methyltransferase gene expression by histone acetylation and methyl-CpG binding proteins. , 2005, Molecular cancer therapeutics.

[23]  S. Nakasu,et al.  Immunohistochemical study for O6-methylguanine-DNA methyltransferase in the non-neoplastic and neoplastic components of gliomas , 2004, Journal of Neuro-Oncology.

[24]  W. Abdullah.  Pediatr Blood Cancer , 2004 .

[25]  B. Bataille,et al.  Correlation of Clinical Features and Methylation Status of MGMT Gene Promoter in Glioblastomas , 2004, Journal of Neuro-Oncology.

[26]  Luca Regli,et al.  Clinical Trial Substantiates the Predictive Value of O-6-Methylguanine-DNA Methyltransferase Promoter Methylation in Glioblastoma Patients Treated with Temozolomide , 2004, Clinical Cancer Research.

[27]  K. Bhakat,et al.  CpG methylation-dependent repression of the human O6-methylguanine-DNA methyltransferase gene linked to chromatin structure alteration. , 2003, Carcinogenesis.

[28]  F. Wright,et al.  Aberrant promoter methylation of previously unidentified target genes is a common abnormality in medulloblastomas–Implications for tumor biology and potential clinical utility , 2001, Oncogene.

[29]  Scar,et al.  Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. , 2000, The New England journal of medicine.

[30]  M. Berger,et al.  O6-methylguanine-DNA methyltransferase-deficient phenotype in human gliomas: frequency and time to tumor progression after alkylating agent-based chemotherapy. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[31]  J. Herman,et al.  Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. , 1999, Cancer research.

[32]  T. Brent,et al.  Methylation hot spots in the 5' flanking region denote silencing of the O6-methylguanine-DNA methyltransferase gene. , 1997, Cancer research.

[33]  J. Costello,et al.  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 , 1997, Molecular and cellular biology.

[34]  B. Kaina,et al.  Induction of the alkyltransferase (MGMT) gene by DNA damaging agents and the glucocorticoid dexamethasone and comparison with the response of base excision repair genes. , 1996, Carcinogenesis.

[35]  J. Herman,et al.  Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[36]  G. Margison,et al.  Inter- and intracellular heterogeneity of O6-alkylguanine-DNA alkyltransferase expression in human brain tumors: possible significance in nitrosourea therapy. , 1996, Carcinogenesis.

[37]  B. Kaina,et al.  Inducibility of the DNA repair gene encoding O6-methylguanine-DNA methyltransferase in mammalian cells by DNA-damaging treatments , 1991, Molecular and cellular biology.

[38]  A. Fornace,et al.  Expression of the O6-methylguanine-DNA methyltransferase gene MGMT in MER+ and MER- human tumor cells. , 1990, Cancer research.

[39]  Audrey E. Evans,et al.  The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: Results of a randomized trial , 1989, Journal of Neuro-Oncology.

[40]  J. Wolff,et al.  Aberrant MGMT (O6-methylguanine-DNA methyltransferase) promoter methylation in choroid plexus tumors , 2008, Journal of Neuro-Oncology.

[41]  W. Remmele,et al.  Comparative histological, histochemical, immunohistochemical and biochemical studies on oestrogen receptors, lectin receptors, and Barr bodies in human breast cancer , 2004, Virchows Archiv A.

[42]  M. Citron,et al.  Intracellular localization and intercellular heterogeneity of the human DNA repair protein O6-methylguanine-DNA methyltransferase , 1996, Cancer Chemotherapy and Pharmacology.