Spatial concordance of DNA methylation classification in diffuse glioma

Autor: Philip C. De Witt Hamer, Petra J. W. Pouwels, W Pieter Vandertop, Frederik Barkhof, Otto S. Hoekstra, Kevin J. Anderson, Sunit Das, Annemieke J.M. Rozemuller, Niels Verburg, Pieter Wesseling, Ronald Boellaard, Michael D. Taylor, Jeroen A.M. Beliën, Jaap C. Reijneveld, Roel G.W. Verhaak, Maqsood Yaqub, Joseph F. Costello, Kevin C. Johnson, Adriaan A. Lammertsma, Floris P. Barthel, Thomas Koopman
Přispěvatelé: Neurosurgery, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, CCA - Imaging and biomarkers, AMS - Tissue Function & Regeneration, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Neuroinfection & -inflammation, Neurology, Amsterdam Neuroscience - Neurodegeneration, Pathology, Amsterdam Neuroscience - Neurovascular Disorders, Amsterdam Neuroscience - Systems & Network Neuroscience, CCA - Cancer Treatment and Quality of Life, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Neuro-Oncology, 23(12), 2054-2065. Oxford University Press
Verburg, N, Barthel, F P, Anderson, K J, Johnson, K C, Koopman, T, Yaqub, M M, Hoekstra, O S, Lammertsma, A A, Barkhof, F, Pouwels, P J W, Reijneveld, J C, Rozemuller, A J M, Beliën, J A M, Boellaard, R, Taylor, M D, Das, S, Costello, J F, Vandertop, W P, Wesseling, P, de Witt Hamer, P C & Verhaak, R G W 2021, ' Spatial concordance of DNA methylation classification in diffuse glioma ', Neuro-Oncology, vol. 23, no. 12, pp. 2054-2065 . https://doi.org/10.1093/neuonc/noab134
Neuro-Oncology, vol 23, iss 12
Neuro-oncology, 23(12), 2054-2065. Oxford University Press
Neuro-Oncology
ISSN: 1522-8517
Popis: 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.
Databáze: OpenAIRE
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