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Keywords {🔍}

methylation, mgmt, glioblastoma, model, probes, article, promoter, google, scholar, hmk, cpg, gene, classification, status, methylated, fig, prediction, supplementary, pubmed, cimp, mgmtstp, cas, glioma, patients, data, cancer, outcome, datasets, expression, samples, dna, analysis, based, grade, msp, cpgs, clinical, anaplastic, unmethylated, survival, island, iii, temozolomide, information, treated, dataset, values, predictive, cohort, tumors,

Topics {✒️}

edema/cellular invasion mri-phenotypes o6-methylguanine-dna methyltransferase t-glioma-ii/iii datasets basically real-time methylation-specific pcr dna damage o6-methylguanine t-glioma-ii/iii datasets o6-methylguanine methyltransferase classic methylation-specific pcr external data-sets suggests dna-repair gene mgmt methylation-specific pyrosequencing-based vb-glioma-iii samples analyzed jocelyne bloch chemo-radiotherapy-treated glioblastoma patients van den bent hm-27k dna methylation t-glioma-ii/iii t-glioma ii/iii parametric smirnov–kolmogorov test log-likelihood ratio test mgmt-stp27-based outcome prediction vb-glioma-iii data pairwise quantile-quantile representation expression-based glioblastoma subtypes hm-450k beadarray platform logit-transformed response fitted wald-based confidence intervals intriguingly distinct behavior article download pdf location-specific cpg methylation vb-glioma-iii dataset vb-glioma-iii datasets grade ii/iii glioma msp-based methylation classification hm-450k methylation data standard chemo-radiotherapy comprised hm-27k data dna methylation analysis hm-27k information consisted pierre-yves dietrich hm-27k data revealed cimp-negative patient subpopulation cimp-negative tumors exhibited roger stupp & monika dna methylome data ms-mlpa methylation calls methylation-specific pcr respective glioblastoma-derived spheres ms-pseq-based prediction methylation-specific pyrosequencing

Questions {❓}

• Weller M, Stupp R, Reifenberger G et al (2010) MGMT promoter methylation in malignant gliomas: ready for personalized medicine?

Schema {🗺️}

WebPage:
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         headline: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
         description:The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene is an important predictive biomarker for benefit from alkylating agent therapy in glioblastoma. Recent studies in anaplastic glioma suggest a prognostic value for MGMT methylation. Investigation of pathogenetic and epigenetic features of this intriguingly distinct behavior requires accurate MGMT classification to assess high throughput molecular databases. Promoter methylation-mediated gene silencing is strongly dependent on the location of the methylated CpGs, complicating classification. Using the HumanMethylation450 (HM-450K) BeadChip interrogating 176 CpGs annotated for the MGMT gene, with 14 located in the promoter, two distinct regions in the CpG island of the promoter were identified with high importance for gene silencing and outcome prediction. A logistic regression model (MGMT-STP27) comprising probes cg1243587 and cg12981137 provided good classification properties and prognostic value (kappa = 0.85; log-rank p < 0.001) using a training-set of 63 glioblastomas from homogenously treated patients, for whom MGMT methylation was previously shown to be predictive for outcome based on classification by methylation-specific PCR. MGMT-STP27 was successfully validated in an independent cohort of chemo-radiotherapy-treated glioblastoma patients (n = 50; kappa = 0.88; outcome, log-rank p < 0.001). Lower prevalence of MGMT methylation among CpG island methylator phenotype (CIMP) positive tumors was found in glioblastomas from The Cancer Genome Atlas than in low grade and anaplastic glioma cohorts, while in CIMP-negative gliomas MGMT was classified as methylated in approximately 50 % regardless of tumor grade. The proposed MGMT-STP27 prediction model allows mining of datasets derived on the HM-450K or HM-27K BeadChip to explore effects of distinct epigenetic context of MGMT methylation suspected to modulate treatment resistance in different tumor types.
         datePublished:2012-07-19T00:00:00Z
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            MSP
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      headline: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
      description:The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene is an important predictive biomarker for benefit from alkylating agent therapy in glioblastoma. Recent studies in anaplastic glioma suggest a prognostic value for MGMT methylation. Investigation of pathogenetic and epigenetic features of this intriguingly distinct behavior requires accurate MGMT classification to assess high throughput molecular databases. Promoter methylation-mediated gene silencing is strongly dependent on the location of the methylated CpGs, complicating classification. Using the HumanMethylation450 (HM-450K) BeadChip interrogating 176 CpGs annotated for the MGMT gene, with 14 located in the promoter, two distinct regions in the CpG island of the promoter were identified with high importance for gene silencing and outcome prediction. A logistic regression model (MGMT-STP27) comprising probes cg1243587 and cg12981137 provided good classification properties and prognostic value (kappa = 0.85; log-rank p < 0.001) using a training-set of 63 glioblastomas from homogenously treated patients, for whom MGMT methylation was previously shown to be predictive for outcome based on classification by methylation-specific PCR. MGMT-STP27 was successfully validated in an independent cohort of chemo-radiotherapy-treated glioblastoma patients (n = 50; kappa = 0.88; outcome, log-rank p < 0.001). Lower prevalence of MGMT methylation among CpG island methylator phenotype (CIMP) positive tumors was found in glioblastomas from The Cancer Genome Atlas than in low grade and anaplastic glioma cohorts, while in CIMP-negative gliomas MGMT was classified as methylated in approximately 50 % regardless of tumor grade. The proposed MGMT-STP27 prediction model allows mining of datasets derived on the HM-450K or HM-27K BeadChip to explore effects of distinct epigenetic context of MGMT methylation suspected to modulate treatment resistance in different tumor types.
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      dateModified:2012-07-19T00:00:00Z
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      pageEnd:560
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         MGMT
         DNA methylation
         MSP
         Infinium methylation platform
         Prediction model
         Pathology
         Neurosciences
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         name:National Center of Competence in Research Molecular Oncology, ISREC-SV-EPFL, Lausanne, Switzerland
         type:PostalAddress
      name:Centre Hospitalier Universitaire Vaudois (CHUV BH19-110)
      address:
         name:Department of Neurosurgery, Laboratory of Brain Tumor Biology and Genetics, Centre Hospitalier Universitaire Vaudois (CHUV BH19-110), Lausanne, Switzerland
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Pierre Bady
      affiliation:
            name:Lausanne University Hospital
            address:
               name:Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
               type:PostalAddress
            type:Organization
            name:Swiss Institute for Bioinformatics
            address:
               name:Bioinformatics Core Facility, Swiss Institute for Bioinformatics, Lausanne, Switzerland
               type:PostalAddress
            type:Organization
            name:Lausanne University Hospital
            address:
               name:Département de Formation et de recherche, Lausanne University Hospital, Lausanne, Switzerland
               type:PostalAddress
            type:Organization
      name:Davide Sciuscio
      affiliation:
            name:Lausanne University Hospital
            address:
               name:Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
               type:PostalAddress
            type:Organization
      name:Annie-Claire Diserens
      affiliation:
            name:Lausanne University Hospital
            address:
               name:Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
               type:PostalAddress
            type:Organization
      name:Jocelyne Bloch
      affiliation:
            name:Lausanne University Hospital
            address:
               name:Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
               type:PostalAddress
            type:Organization
      name:Martin J. van den Bent
      affiliation:
            name:Erasmus Medical Center
            address:
               name:Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
               type:PostalAddress
            type:Organization
      name:Christine Marosi
      affiliation:
            name:Medical University of Vienna
            address:
               name:Medical University of Vienna, Vienna, Austria
               type:PostalAddress
            type:Organization
      name:Pierre-Yves Dietrich
      affiliation:
            name:University Hospital Geneva
            address:
               name:University Hospital Geneva, Geneva, Switzerland
               type:PostalAddress
            type:Organization
      name:Michael Weller
      affiliation:
            name:University of Tübingen
            address:
               name:Department of Neurology, University of Tübingen, Tübingen, Germany
               type:PostalAddress
            type:Organization
            name:University Hospital Zurich
            address:
               name:Department of Neurology, University Hospital Zurich, Zurich, Switzerland
               type:PostalAddress
            type:Organization
      name:Luigi Mariani
      affiliation:
            name:Inselspital Berne
            address:
               name:Department of Neurosurgery, Inselspital Berne, Berne, Switzerland
               type:PostalAddress
            type:Organization
      name:Frank L. Heppner
      affiliation:
            name:University Hospital Zurich
            address:
               name:Department of Neuropathology, University Hospital Zurich, Zurich, Switzerland
               type:PostalAddress
            type:Organization
      name:David R. Mcdonald
      affiliation:
            name:London Regional Cancer Program London Health Sciences Centre, University of Western Ontario
            address:
               name:Neurology and Neuro-Oncology, London Regional Cancer Program London Health Sciences Centre, University of Western Ontario, London, Canada
               type:PostalAddress
            type:Organization
      name:Denis Lacombe
      affiliation:
            name:EORTC Headquaters
            address:
               name:EORTC Headquaters, Brussels, Belgium
               type:PostalAddress
            type:Organization
      name:Roger Stupp
      affiliation:
            name:Lausanne University Hospital
            address:
               name:Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
               type:PostalAddress
            type:Organization
      name:Mauro Delorenzi
      affiliation:
            name:Swiss Institute for Bioinformatics
            address:
               name:Bioinformatics Core Facility, Swiss Institute for Bioinformatics, Lausanne, Switzerland
               type:PostalAddress
            type:Organization
            name:Lausanne University Hospital
            address:
               name:Département de Formation et de recherche, Lausanne University Hospital, Lausanne, Switzerland
               type:PostalAddress
            type:Organization
            name:ISREC-SV-EPFL
            address:
               name:National Center of Competence in Research Molecular Oncology, ISREC-SV-EPFL, Lausanne, Switzerland
               type:PostalAddress
            type:Organization
      name:Monika E. Hegi
      affiliation:
            name:Lausanne University Hospital
            address:
               name:Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
               type:PostalAddress
            type:Organization
            name:ISREC-SV-EPFL
            address:
               name:National Center of Competence in Research Molecular Oncology, ISREC-SV-EPFL, Lausanne, Switzerland
               type:PostalAddress
            type:Organization
            name:Centre Hospitalier Universitaire Vaudois (CHUV BH19-110)
            address:
               name:Department of Neurosurgery, Laboratory of Brain Tumor Biology and Genetics, Centre Hospitalier Universitaire Vaudois (CHUV BH19-110), Lausanne, Switzerland
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
      name:Bioinformatics Core Facility, Swiss Institute for Bioinformatics, Lausanne, Switzerland
      name:Département de Formation et de recherche, Lausanne University Hospital, Lausanne, Switzerland
      name:Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
      name:Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
      name:Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
      name:Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
      name:Medical University of Vienna, Vienna, Austria
      name:University Hospital Geneva, Geneva, Switzerland
      name:Department of Neurology, University of Tübingen, Tübingen, Germany
      name:Department of Neurology, University Hospital Zurich, Zurich, Switzerland
      name:Department of Neurosurgery, Inselspital Berne, Berne, Switzerland
      name:Department of Neuropathology, University Hospital Zurich, Zurich, Switzerland
      name:Neurology and Neuro-Oncology, London Regional Cancer Program London Health Sciences Centre, University of Western Ontario, London, Canada
      name:EORTC Headquaters, Brussels, Belgium
      name:Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
      name:Bioinformatics Core Facility, Swiss Institute for Bioinformatics, Lausanne, Switzerland
      name:Département de Formation et de recherche, Lausanne University Hospital, Lausanne, Switzerland
      name:National Center of Competence in Research Molecular Oncology, ISREC-SV-EPFL, Lausanne, Switzerland
      name:Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
      name:National Center of Competence in Research Molecular Oncology, ISREC-SV-EPFL, Lausanne, Switzerland
      name:Department of Neurosurgery, Laboratory of Brain Tumor Biology and Genetics, Centre Hospitalier Universitaire Vaudois (CHUV BH19-110), Lausanne, Switzerland

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