Topographical Mapping of 436 Newly Diagnosed IDH Wildtype Glioblastoma With vs. Without MGMT Promoter Methylation

Introduction: O6-methylguanine-methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase (IDH) mutation status are important prognostic factors for patients with glioblastoma. There are conflicting reports about a differential topographical distribution of glioblastoma with vs. with...

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Main Authors: Fatih Incekara, Sebastian R. van der Voort, Hendrikus J. Dubbink, Peggy N. Atmodimedjo, Rishi Nandoe Tewarie, Geert Lycklama, Arnaud J. P. E. Vincent, Johan M. Kros, Stefan Klein, Martin van den Bent, Marion Smits
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-05-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/article/10.3389/fonc.2020.00596/full
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spelling doaj-098352aa8b004aad8000017761ad82732020-11-25T02:05:11ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-05-011010.3389/fonc.2020.00596529909Topographical Mapping of 436 Newly Diagnosed IDH Wildtype Glioblastoma With vs. Without MGMT Promoter MethylationFatih Incekara0Fatih Incekara1Sebastian R. van der Voort2Hendrikus J. Dubbink3Peggy N. Atmodimedjo4Rishi Nandoe Tewarie5Geert Lycklama6Arnaud J. P. E. Vincent7Johan M. Kros8Stefan Klein9Martin van den Bent10Marion Smits11Department of Neurosurgery, Brain Tumor Center, Erasmus MC - University Medical Center Rotterdam, Rotterdam, NetherlandsDepartment of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, NetherlandsDepartment of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, NetherlandsDepartment of Pathology, Brain Tumor Center at Erasmus MC Cancer Institute, Rotterdam, NetherlandsDepartment of Pathology, Brain Tumor Center at Erasmus MC Cancer Institute, Rotterdam, NetherlandsDepartment of Neurosurgery, Haaglanden MC, The Hague, NetherlandsDepartment of Radiology, Haaglanden MC, The Hague, NetherlandsDepartment of Neurosurgery, Brain Tumor Center, Erasmus MC - University Medical Center Rotterdam, Rotterdam, NetherlandsDepartment of Pathology, Brain Tumor Center at Erasmus MC Cancer Institute, Rotterdam, NetherlandsDepartment of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, NetherlandsDepartment of Neurology, Brain Tumor Center, Erasmus MC Cancer Institute, Rotterdam, NetherlandsDepartment of Radiology and Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, NetherlandsIntroduction: O6-methylguanine-methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase (IDH) mutation status are important prognostic factors for patients with glioblastoma. There are conflicting reports about a differential topographical distribution of glioblastoma with vs. without MGMT promoter methylation, possibly caused by molecular heterogeneity in glioblastoma populations. We initiated this study to re-evaluate the topographical distribution of glioblastoma with vs. without MGMT promoter methylation in light of the updated WHO 2016 classification.Methods: Preoperative T2-weighted/FLAIR and postcontrast T1-weighted MRI scans of patients aged 18 year or older with IDH wildtype glioblastoma were collected. Tumors were semi-automatically segmented, and the topographical distribution between glioblastoma with vs. without MGMT promoter methylation was visualized using frequency heatmaps. Then, voxel-wise differences were analyzed using permutation testing with Threshold Free Cluster Enhancement.Results: Four hundred thirty-six IDH wildtype glioblastoma patients were included; 211 with and 225 without MGMT promoter methylation. Visual examination suggested that when compared with MGMT unmethylated glioblastoma, MGMT methylated glioblastoma were more frequently located near bifrontal and left occipital periventricular area and less frequently near the right occipital periventricular area. Statistical analyses, however, showed no significant difference in topographical distribution between MGMT methylated vs. MGMT unmethylated glioblastoma.Conclusions: This study re-evaluated the topographical distribution of MGMT promoter methylation in 436 newly diagnosed IDH wildtype glioblastoma, which is the largest homogenous IDH wildtype glioblastoma population to date. There was no statistically significant difference in anatomical localization between MGMT methylated vs. unmethylated IDH wildtype glioblastoma.https://www.frontiersin.org/article/10.3389/fonc.2020.00596/fullglioblastomaMGMTheatmapatlaslocalization
collection DOAJ
language English
format Article
sources DOAJ
author Fatih Incekara
Fatih Incekara
Sebastian R. van der Voort
Hendrikus J. Dubbink
Peggy N. Atmodimedjo
Rishi Nandoe Tewarie
Geert Lycklama
Arnaud J. P. E. Vincent
Johan M. Kros
Stefan Klein
Martin van den Bent
Marion Smits
spellingShingle Fatih Incekara
Fatih Incekara
Sebastian R. van der Voort
Hendrikus J. Dubbink
Peggy N. Atmodimedjo
Rishi Nandoe Tewarie
Geert Lycklama
Arnaud J. P. E. Vincent
Johan M. Kros
Stefan Klein
Martin van den Bent
Marion Smits
Topographical Mapping of 436 Newly Diagnosed IDH Wildtype Glioblastoma With vs. Without MGMT Promoter Methylation
Frontiers in Oncology
glioblastoma
MGMT
heatmap
atlas
localization
author_facet Fatih Incekara
Fatih Incekara
Sebastian R. van der Voort
Hendrikus J. Dubbink
Peggy N. Atmodimedjo
Rishi Nandoe Tewarie
Geert Lycklama
Arnaud J. P. E. Vincent
Johan M. Kros
Stefan Klein
Martin van den Bent
Marion Smits
author_sort Fatih Incekara
title Topographical Mapping of 436 Newly Diagnosed IDH Wildtype Glioblastoma With vs. Without MGMT Promoter Methylation
title_short Topographical Mapping of 436 Newly Diagnosed IDH Wildtype Glioblastoma With vs. Without MGMT Promoter Methylation
title_full Topographical Mapping of 436 Newly Diagnosed IDH Wildtype Glioblastoma With vs. Without MGMT Promoter Methylation
title_fullStr Topographical Mapping of 436 Newly Diagnosed IDH Wildtype Glioblastoma With vs. Without MGMT Promoter Methylation
title_full_unstemmed Topographical Mapping of 436 Newly Diagnosed IDH Wildtype Glioblastoma With vs. Without MGMT Promoter Methylation
title_sort topographical mapping of 436 newly diagnosed idh wildtype glioblastoma with vs. without mgmt promoter methylation
publisher Frontiers Media S.A.
series Frontiers in Oncology
issn 2234-943X
publishDate 2020-05-01
description Introduction: O6-methylguanine-methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase (IDH) mutation status are important prognostic factors for patients with glioblastoma. There are conflicting reports about a differential topographical distribution of glioblastoma with vs. without MGMT promoter methylation, possibly caused by molecular heterogeneity in glioblastoma populations. We initiated this study to re-evaluate the topographical distribution of glioblastoma with vs. without MGMT promoter methylation in light of the updated WHO 2016 classification.Methods: Preoperative T2-weighted/FLAIR and postcontrast T1-weighted MRI scans of patients aged 18 year or older with IDH wildtype glioblastoma were collected. Tumors were semi-automatically segmented, and the topographical distribution between glioblastoma with vs. without MGMT promoter methylation was visualized using frequency heatmaps. Then, voxel-wise differences were analyzed using permutation testing with Threshold Free Cluster Enhancement.Results: Four hundred thirty-six IDH wildtype glioblastoma patients were included; 211 with and 225 without MGMT promoter methylation. Visual examination suggested that when compared with MGMT unmethylated glioblastoma, MGMT methylated glioblastoma were more frequently located near bifrontal and left occipital periventricular area and less frequently near the right occipital periventricular area. Statistical analyses, however, showed no significant difference in topographical distribution between MGMT methylated vs. MGMT unmethylated glioblastoma.Conclusions: This study re-evaluated the topographical distribution of MGMT promoter methylation in 436 newly diagnosed IDH wildtype glioblastoma, which is the largest homogenous IDH wildtype glioblastoma population to date. There was no statistically significant difference in anatomical localization between MGMT methylated vs. unmethylated IDH wildtype glioblastoma.
topic glioblastoma
MGMT
heatmap
atlas
localization
url https://www.frontiersin.org/article/10.3389/fonc.2020.00596/full
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