EGAGenomicsN/Ahttps://ega-archive.org/datasets/EGAD00010002182133EGA dataset EGAD00010002182EGA<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.Spatial concordance of DNA methylation classification in diffuse glioma.Verburg Niels N, Barthel Floris P FP, Anderson Kevin J KJ, Johnson Kevin C KC, Koopman Thomas T, Yaqub Maqsood M MM, Hoekstra Otto S OS, Lammertsma Adriaan A AA, Barkhof Frederik F, Pouwels Petra J W PJW, Reijneveld Jaap C JC, Rozemuller Annemieke J M AJM, Beliën Jeroen A M JAM, Boellaard Ronald R, Taylor Michael D MD, Das Sunit S, Costello Joseph F JF, Vandertop William Peter WP, Wesseling Pieter P, de Witt Hamer Philip C PC, Verhaak Roel G W RGWDNA, DNA methylation maintenance, DNA Methylations, DNA., DNA methylation, Methylations, MethylationDNA methylation maintenance, Malignant Neoplasm, Biopsies, Malignancy, Neoplasms, Benign Neoplasm, Benign Neoplasms, Cancers, DNA Methylations, DNA methylation, Tumor, Malignant, Malignant Neoplasms, Neoplasias, Benign, microarray., Neoplasm, Malignancies, DNA, other neoplasm, Methylations, Neoplasia, Methylation, Cancer, TumorsGlioma 1, Glioma NOS, Glioma (except Nasal glioma, GLM, taxonomy, diffuse, glial tumors, malignant, neuroglial tumor, Systematics, obsolete_glioma, Mixed Glioma, Malignant Glioma, Neuroglial Tumor, DNA Methylations, tumour of the neuroglia, Tumor, Malignant, neoplasm of neuroglia, Classifications, Taxonomies, hierarchies, hierarchy, [M]Glioma NOS (morphologic abnormality), systematics, tumor of the neuroglia, [M]Gliomas (morphologic abnormality), Gliomas, Mixed, Glial Cell Tumor, [M]Glioma NOS, Mixed Gliomas, Glial Tumor, NOS (except Nasal glioma, Taxonomy, DNA methylation maintenance, Neuroglial Neoplasm, glioma (morphologic abnormality), Neuroglial Neoplasms, Glioma NOS (morphologic abnormality), scattered, neuroglial tumour, Glial Cell, Malignant glioma, Neoplasm of the Neuroglia, Tumor of Neuroglia, Glial Neoplasm, DNA methylation, neuroglial neoplasm, tumor of neuroglia, Neoplasm of Neuroglia, glial tumor, no ICD-O subtype, Neoplasms of Neuroglia., Tumor of the Neuroglia, tumour of neuroglia, glial tumour, Glial Cell Tumors, not neoplastic), Gliomas (morphologic abnormality), Malignant Gliomas, Glioma, DNA, glial neoplasm, [M]Gliomas, malignant (morphologic abnormality), glioma, Tumors of Neuroglia, Methylations, neoplasm of the neuroglia, Methylation, TumorsMGC130048, isocitrate dehydrogenase, oligodendroglioma, 3-Dimensional, adult stage, Brain Neoplasms, FBgn0038922, Anaplastic Oligodendrogliomas, Characterization, Suggestion, A4, mNADP-IDH, Mixed Oligodendroglioma-Astrocytoma, Imaging, DNA Methylations, Tumor, congenital defects, fluid, Astrocytomas, Highly, Brain Metastases, aplasia, limitations, Childhood Oligodendroglioma, Classifications, Techniques, hierarchies, hierarchy, Image Reconstruction, Clonal, INTRACRANIAL NEOPL, Method, systematics, analysis, Acquisition, reconstructive surgery, Analysis, tumour of brain, Oligodendroblastomas, study limitations, Effect, adult, glioma of brain, Monoclonal Cellular Population Present, Obtained, CG1216, PICD, Stereotactic Biopsy, gamma sarcoglycan, Cytosolic NADP-isocitrate dehydrogenase, Divorced, Mixed Oligodendroglioma-Ependymoma, No mutation detected, DNA methylation maintenance, IDH-mutant, Observed, brain neoplasms, Molecular, Optical Image Reconstruction, hypoplasia, Brain Malignant Neoplasms, Primary Brain Tumors, D2HGA2, Brain Tumor, Divorces, procedures, DNA methylation, Giant Cell Glioblastoma, Adult, stereotactic biopsy, Adult Oligodendroglioma, NADP(+)-specific ICDH, Astrocytoma, Epigenomic, Monotypic Cells Present, neoplasm of brain, Methodological Studies, Brain Neoplasm, Primary Malignant Brain Tumors, IDPC, grade IV adult Astrocytic tumor, Recurrent Brain Tumor, 3D, gamma-sarcoglycan, Analyzed, Malignancies, RECONSTRUCTION_TYPE, Concordance, IDPM, Tumors, Well Differentiated Oligodendroglioma, Clonality, Oligodendroglioma-Ependymoma, Intracranial Neoplasm, brain neoplasm, Malignant Brain Neoplasms, Brain Benign Neoplasm, DmelCG1216, IDH, Idh, Wildtype Positive, Mixed Oligodendroglioma Ependymoma, familial, RECOVERY, assessment, SG-gamma, Malignant Primary Brain Neoplasms, Systematics, IDP, Confidence, l(3)L3852, Primary Brain Neoplasm, NEOPL BRAIN, Procedure, Giant Cell, Diffuse Glioma, DNA methylation profiling, Anaplastic, Oligodendroglioma-Ependymomas, deformities, 3-dimensional, Clonal Cellular Population Present, results, Primary Brain Tumor, IDCD, Reconstructive Surgery, Diffuse astrocytoma, Taxonomies, Electrical Current, Benign, Brain Benign Neoplasms, Well-Differentiated Oligodendroglioma, idh, primary glioblastoma multiforme, Mixed Oligodendroglioma-Astrocytomas, Brain Malignant Neoplasm, CURRENT, Obtain, Tumor_Purity, Malignant Primary Brain Tumors, sarcoglycan, Mutant, Assessed, Adults, Malignant Brain Neoplasm, atresia, Primary Malignant, TUMCECE, Glioblastoma, CT22171, oligodendroglial tumor, Epigenetic, Cancer of the Brain, spongioblastoma multiforme, Mixed Oligodendroglioma Astrocytoma, Oligodendroblastoma, conclusion, malformations, Heterogeneity, GBM, Benign Neoplasms, tumor of the Brain, Methodological, Presence, gamma (35kDa dystrophin-associated glycoprotein), Methodological Study, Present, WT, wt, Oxalosuccinate decarboxylase, Malignant Neoplasms, Clone, Intracranial, 1.1.1.42, Characterized, DMDA, neoplasm of the brain, Grade IV Astrocytomas, IDH Mutant, brain tumor, Patient, Tumor Purity, DmelCG6439, 35kD dystrophin-associated glycoprotein, Oligodendroglioma-Astrocytomas, anomalies, Oligodendroglioma, Mixed Oligodendroglioma-Ependymomas, Assess, DNA, clone, Epigenetics, other neoplasm, Methylation, EPI, Brain, Account, Brain Tumors, Primary Malignant Brain Neoplasms, SGCG_HUMAN, Procedures, heterogeneity., Effects, taxonomy, IDH-Mutant, Neoplasms, Primary Brain Neoplasms, Cancer of Brain, Benign Neoplasm, Statistical Confidence, Goal, IMAGE, clonality, Analytical, Grade IV, Well-Differentiated Oligodendrogliomas, Malignant, Wildtype Detected, TYPE, Financial Account, DAGA4, adult brain oligodendroglioma, Recurrent Brain Tumors, 3-D, Recurrent, Genetic heterogeneity, Sites, 35DAG, Studies, Frameless Stereotaxy, oligodendroglial neoplasm, glioblastoma, Well Differentiated, defects, MAM, gamma-SG, Giant Cell Glioblastomas, Separated, HEL-216, attenuated, SCG3, Technique, Higher, Current, Site, study, IDHM, Taxonomy, Mri, MRI, In, grade IV adult astrocytic tumor, Genetic, Genetic Heterogeneities, PRESENT, tumour of the Brain, ANALYSIS, Malignancy, Suggest, scattered, astrocytoma, subependymoma, intratumoral, DmelCG7176, Reconstruction, Tumor Cell to Total Cell Ratio Measurement, Study, Neoplasias, Glioblastoma Multiforme, Acquire, PRIMARY BRAIN NEOPL, IDH-NADP, IDH2, Diffuse Astrocytoma, Concordant, Routine, Clients, Monotypic Cell Population Present, Found, heterogeneity, ependymoma, Intratumoral, Grade IV Astrocytoma, Tumor Cells/Total Cells, Methylations, tumor of brain, NEOPL INTRACRANIAL, Cancer, Oligodendrogliomas, grade IV adult astrocytic tumour, Idh-NADP, lumen, Malignant Neoplasm, 35 kDa dystrophin-associated glycoprotein, diffuse, Recovery, ICD-M, space, Benign Brain Neoplasms, Primary, Stereotaxy, Frameless, Client, Wild Type, SGCG, Conclusion, LGMD2C, adult glioblastoma multiforme, Well-Differentiated, agenesis, Adult Oligodendrogliomas, HEL-S-26, Neoplasm, Brain Cancers, Mixed, background, techniques, methylation, Approach, Oligodendroglioma-Astrocytoma, anatomical spaces, Brain Metastase, Childhood Oligodendrogliomas, Intracranial Neoplasms, glioblastoma multiforme, Separation, lumen space, oligodendroglial tumour, brain neoplasm (disease), Assessment, AL023049, DMDA1, CG7176, Clinical Classification, Separations, INV, Glioblastomas, Wildtype, Salvage, Heterogeneities, Childhood, Cancers, Brain Cancer, introduction, Wildtype Finding, High, recover, Monotypic, birth defects, SCARMD2, Anaplastic Oligodendroglioma, Benign Brain Neoplasm, brain tumour, variable, Neoplasia, methodologyfalseFRONTIER DNA methylationTumor biopsies profiled by DNA methylation array2021-08-06 08:12:52EGAD00010002182960634049406EGAC00001002214EGAS00001005434