ArticleNeuro-oncology2014
The combination of IDH1 mutations and MGMT methylation status predicts survival in glioblastoma better than either IDH1 or MGMT alone.
Open access · bronzeAbstract read
In one paragraph
Article in Neuro-oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 7 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 7 pooled it
9.3field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
122 citing papers in PubMed, 7 syntheses or guidelines pooled it, 209 citations in OpenAlex.
- Pooled it
- A systematic review of high impact CpG sites and regions for MGMT methylation in glioblastoma [A systematic review of MGMT methylation in GBM].BMC neurology · 2024Pooled it
- Molecular Biomarker Testing for the Diagnosis of Diffuse Gliomas.Archives of pathology & laboratory medicine · 2022Guideline
- High CD133 Expression Is Associated with Worse Prognosis in Patients with Glioblastoma.Molecular neurobiology · 2016Pooled it
- Assessment of the Association between Isocitrate Dehydrogenase 1 Mutation and Mortality Risk of Glioblastoma Patients.Molecular neurobiology · 2016Pooled it
- Isocitrate Dehydrogenase (IDH)1/2 Mutations as Prognostic Markers in Patients With Glioblastomas.Medicine · 2016Pooled it
- Prognostic role of IDH mutations in gliomas: a meta-analysis of 55 observational studies.Oncotarget · 2015Pooled it
- Phase Ib/II Study of Pamiparib Plus Radiation Therapy and/or Temozolomide in Adult Patients with Treatment-Naïve or Recurrent/Refractory Glioblastoma.Current oncology (Toronto, Ont.) · 2025Trial
- Effects of 5-ALA dose on resection of glioblastoma.Journal of neuro-oncology · 2019Trial
- Spatially identifying regions of tumor recurrence in patients with suspected recurrent glioma using physiologic MRI and machine learning.NPJ digital medicine · 2026Article
- Glioblastoma survival prediction through MRI and clinical data integration with transfer learning.International journal of computer assisted radiology and surgery · 2026Article
- Redefining the immune microenvironment of gliomas in the era of single-cell genomics.Neuro-oncology advances · 2026Review
- Development and Validation of an Early Recurrence Prediction Model for High-Grade Glioma Integrating Temporalis Muscle and Tumor Features: Exploring the Prognostic Value of Temporalis Muscle.Journal of imaging informatics in medicine · 2026Article
- Machine-Learning-Based Prediction of Clinical Outcomes in Gliomas Using Glycomic Features.Computational and structural biotechnology journal · 2026Article
- Case Report: Beyond two years: a neurosurgical review of prolonged survival and late recurrence in IDH-wildtype GBM.Frontiers in surgery · 2026Article
- RNaseH2 inhibition potentiates temozolomide response in patient derived glioblastoma cells.Scientific reports · 2025Article
- GlioSurv: interpretable transformer for multimodal, individualized survival prediction in diffuse glioma.NPJ digital medicine · 2025Article
- Beyond the Promoter: Total MGMT Gene Methylation Modulates Response to DNA-Alkylating Agents in Glioma.Molecular cancer therapeutics · 2025Article
- Is modulation of immune checkpoints on glioblastoma-infiltrating myeloid cells a viable therapeutic strategy?Neuro-oncology · 2025Review
- Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 3 countries.
Remco J MolenaarDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
Dagmar VerbaanDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
Simona LambaDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
Carlo ZanonDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
Judith W M JeukenDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
Sandra H E Boots-SprengerDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
Pieter WesselingDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
Theo J M HulsebosDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
Dirk TroostDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
Angela A van TilborgDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
Sieger LeenstraDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
W Peter VandertopDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
Alberto BardelliDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
Cornelis J F van NoordenDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
Fonnet E BleekerDepartment of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (R.J.M., C.J.F.v.N.); Neurosurgical Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands (F.E.B., D.V., W.P.V.); Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy (S.La., C.Z., A.B., F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands (J.W.M.J., S.H.E.B.-S., P.W.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (P.W.); Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (T.J.M.H.); Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (D.T., A.A.v.T.); Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands (W.P.V.); Department of Neurosurgery, St. Elisabeth Hospital Tilburg, The Netherlands (S.Le.); Department of Neurosurgery, Erasmus Medical Center, Rotterdam, The Netherlands (S.Le.); FIRC Institute of Molecular Oncology, Milan, Italy (A.B.)Present affiliation: Department of Clinical Genetics, Academic Medical Center and University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (F.E.B.); Department of Pathology, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (A.A.v.T.); Department of Neurology, Radboud University Medical Centre Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands (S.H.E.B.-S.); Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands (J.W.M.J.).
Amsterdam UMC Location VUmc · NLAcademic Medical Center · NLRadboud University Medical Center · NLRadboud University Nijmegen · NLAmsterdam Neuroscience · NL
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenetic and epigenetic profiling of glioblastomas has provided a comprehensive list of altered cancer genes of which only O(6)-methylguanine-methyltransferase (MGMT) methylation is used thus far as a predictive marker in a clinical setting. We investigated the prognostic significance of genetic and epigenetic alterations in glioblastoma patients.
methodsWe screened 98 human glioblastoma samples for genetic and epigenetic alterations in 10 genes and chromosomal loci by PCR and multiplex ligation-dependent probe amplification (MLPA). We tested the association between these genetic and epigenetic alterations and glioblastoma patient survival. Subsequently, we developed a 2-gene survival predictor.
resultsMultivariate analyses revealed that mutations in isocitrate dehydrogenase 1 (IDH1), promoter methylation of MGMT, irradiation dosage, and Karnofsky Performance Status (KFS) were independent prognostic factors. A 2-gene predictor for glioblastoma survival was generated. Based on the genetic and epigenetic status of IDH1 and MGMT, glioblastoma patients were stratified into 3 clinically different genotypes: glioblastoma patients with IDH1mt/MGMTmet had the longest survival, followed by patients with IDH1mt/MGMTunmet or IDH1wt/MGMTmet, and patients with IDH1wt/MGMTunmet had the shortest survival. This 2-gene predictor was an independent prognostic factor and performed significantly better in predicting survival than either IDH1 mutations or MGMT methylation alone. The predictor was validated in 3 external datasets. DISCUSSION: The combination of IDH1 mutations and MGMT methylation outperforms either IDH1 mutations or MGMT methylation alone in predicting survival of glioblastoma patients. This information will help to increase our understanding of glioblastoma biology, and it may be helpful for baseline comparisons in future clinical trials.
Indexed as
MutationAdultAgedAged, 80 and overBrain NeoplasmsDNA MethylationDNA Modification MethylasesDNA Repair EnzymesEpigenesis, GeneticFemaleGlioblastomaHumansIsocitrate DehydrogenaseMaleMiddle AgedSurvival AnalysisDNA Modification MethylasesDNA Repair EnzymesIDH1 protein, humanIsocitrate DehydrogenaseMGMT protein, humanTumor Suppressor Proteinsgenetic and epigeneticglioblastomaIDH1MGMTsurvival prediction
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