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Tytuł:
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Spatial concordance of DNA methylation classification in diffuse glioma.
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Autorzy:
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Verburg N; Department of Neurosurgery, Amsterdam UMC, Vrije Universiteit, and Brain Tumor Centre, Cancer Center Amsterdam, Amsterdam, the Netherlands.; Cambridge Brain Tumor Imaging Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Barthel FP; The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
Anderson KJ; The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
Johnson KC; The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
Koopman T; Department of Radiology and Nuclear Medicine, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.
Yaqub MM; Department of Radiology and Nuclear Medicine, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.
Hoekstra OS; Department of Radiology and Nuclear Medicine, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.
Lammertsma AA; Department of Radiology and Nuclear Medicine, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.
Barkhof F; Department of Radiology and Nuclear Medicine, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.; UCL Institutes of Neurology and Healthcare Engineering, London, UK.
Pouwels PJW; Department of Radiology and Nuclear Medicine, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.
Reijneveld JC; Department of Neurology, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.; Department of Neurology, Stichting Epilepsie Instellingen Nederland, Heemstede, the Netherlands.
Rozemuller AJM; Department of Pathology, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.; Princess Máxima Centre for Paediatric Oncology, Utrecht, the Netherlands.
Beliën JAM; Department of Pathology, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.
Boellaard R
Taylor MD; Department of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario, Canada.; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Kids, Toronto, Ontario, Canada.
Das S; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Kids, Toronto, Ontario, Canada.; Division of Neurosurgery, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Costello JF; Department of Neurological Surgery, UCSF, San Francisco, California, USA.
Vandertop WP; Department of Neurosurgery, Amsterdam UMC, Vrije Universiteit, and Brain Tumor Centre, Cancer Center Amsterdam, Amsterdam, the Netherlands.
Wesseling P; Department of Pathology, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.
de Witt Hamer PC; Department of Neurosurgery, Amsterdam UMC, Vrije Universiteit, and Brain Tumor Centre, Cancer Center Amsterdam, Amsterdam, the Netherlands.
Verhaak RGW; Department of Neurosurgery, Amsterdam UMC, Vrije Universiteit, and Brain Tumor Centre, Cancer Center Amsterdam, Amsterdam, the Netherlands.; The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
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Źródło:
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Neuro-oncology [Neuro Oncol] 2021 Dec 01; Vol. 23 (12), pp. 2054-2065.
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Typ publikacji:
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Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
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Język:
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English
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Imprint Name(s):
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Publication: 2010- : Oxford : Oxford University Press
Original Publication: 1999-<2002> : Charlottesville, VA : Carden Jennings Pub.,
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MeSH Terms:
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Brain Neoplasms*/diagnostic imaging
Brain Neoplasms*/genetics
Glioma*/diagnostic imaging
Glioma*/genetics
Oligodendroglioma*
Adult ; DNA Methylation ; Humans ; Isocitrate Dehydrogenase/genetics ; Mutation
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Grant Information:
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P50 CA097257 United States CA NCI NIH HHS; R01 CA237208 United States CA NCI NIH HHS; R01 CA190121 United States CA NCI NIH HHS; R21 NS114873 United States NS NINDS NIH HHS; R01 CA244838 United States CA NCI NIH HHS; P30 CA034196 United States CA NCI NIH HHS; K99 CA226387 United States CA NCI NIH HHS
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Contributed Indexing:
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Keywords: DNA methylation classification; epigenetics; glioma; imaging; intratumoral heterogeneity
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Substance Nomenclature:
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EC 1.1.1.41 (Isocitrate Dehydrogenase)
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Entry Date(s):
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Date Created: 20210528 Date Completed: 20220119 Latest Revision: 20220510
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Update Code:
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20240105
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PubMed Central ID:
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PMC8643482
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DOI:
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10.1093/neuonc/noab134
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PMID:
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34049406
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Background: Intratumoral heterogeneity is a hallmark of diffuse gliomas. DNA methylation profiling is an emerging approach in the clinical classification of brain tumors. The goal of this study is to investigate the effects of intratumoral heterogeneity on classification confidence.
Methods: We used neuronavigation to acquire 133 image-guided and spatially separated stereotactic biopsy samples from 16 adult patients with a diffuse glioma (7 IDH-wildtype and 2 IDH-mutant glioblastoma, 6 diffuse astrocytoma, IDH-mutant and 1 oligodendroglioma, IDH-mutant and 1p19q codeleted), which we characterized using DNA methylation arrays. Samples were obtained from regions with and without abnormalities on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery MRI. Methylation profiles were analyzed to devise a 3-dimensional reconstruction of (epi)genetic heterogeneity. Tumor purity was assessed from clonal methylation sites.
Results: Molecular aberrations indicated that tumor was found outside imaging abnormalities, underlining the infiltrative nature of this tumor and the limitations of current routine imaging modalities. We demonstrate that tumor purity is highly variable between samples and explains a substantial part of apparent epigenetic spatial heterogeneity. We observed that DNA methylation subtypes are often, but not always, conserved in space taking tumor purity and prediction accuracy into account.
Conclusion: Our results underscore the infiltrative nature of diffuse gliomas and suggest that DNA methylation subtypes are relatively concordant in this tumor type, although some heterogeneity exists.
(© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
