title: Malignant Transformation of a Dysembryoplastic Neuroepithelial Tumor (DNET) Characterized by Genome-Wide Methylation Analysis.
abstract: Dysembryoplastic neuroepithelial tumors (DNET) are considered to be rare, benign, and associated with chronic epilepsy. We present the case of a 28-year-old man with a history of epilepsy since age 12. Surgery of an occipital cortical lesion in 2009 revealed a DNET. Five years later, a recurrent tumor at the edge of the resection cavity was removed, and the tissue underwent an intensive diagnostic workup. The first tumor was unequivocally characterized as a DNET, but neuropathological diagnostics of the recurrent tumor revealed a glioblastoma. After 6 months, another recurrent tumor was detected next to the location of the original tumor, and this was also resected. An Illumina 450 K beadchip methylation array was performed to characterize all of the tumors. The methylation profile of these tumors significantly differed from other glioblastoma and epilepsy-associated tumor profiles and revealed a DNET-like methylation profile. Thus, molecular characterization of these recurrent tumors suggests malignant transformation of a previously benign DNET. We found increased copy number changes in the recurrent DNET tumors after malignant transformation. Modern high-throughput analysis adds essential molecular information in addition to standard histopathology for proper identification of rare brain tumors that present with an unusual clinical course.
authors.affiliation: From the Department of Neurosurgery (DHH, WM, PF, JG, AW), Department of Pathology, Institute of Neuropathology (OS), Department of Neurosurgery, Epilepsy Center (MH), and Department of Neuroradiology (HU), Medical Center - University of Freiburg, Freiburg, Germany; and Department of Neuropathology, University Heidelberg, Im Neuenheimer Feld 224 and German Cancer Consortium (DKTK), CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany (DC, DS).
authors.forename: Dieter Henrik
authors.initials: DH
authors.lastname: Heiland
authors.affiliation: From the Department of Neurosurgery (DHH, WM, PF, JG, AW), Department of Pathology, Institute of Neuropathology (OS), Department of Neurosurgery, Epilepsy Center (MH), and Department of Neuroradiology (HU), Medical Center - University of Freiburg, Freiburg, Germany; and Department of Neuropathology, University Heidelberg, Im Neuenheimer Feld 224 and German Cancer Consortium (DKTK), CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany (DC, DS).
authors.forename: Ori
authors.initials: O
authors.lastname: Staszewski
authors.affiliation: From the Department of Neurosurgery (DHH, WM, PF, JG, AW), Department of Pathology, Institute of Neuropathology (OS), Department of Neurosurgery, Epilepsy Center (MH), and Department of Neuroradiology (HU), Medical Center - University of Freiburg, Freiburg, Germany; and Department of Neuropathology, University Heidelberg, Im Neuenheimer Feld 224 and German Cancer Consortium (DKTK), CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany (DC, DS).
authors.forename: Martin
authors.initials: M
authors.lastname: Hirsch
authors.affiliation: From the Department of Neurosurgery (DHH, WM, PF, JG, AW), Department of Pathology, Institute of Neuropathology (OS), Department of Neurosurgery, Epilepsy Center (MH), and Department of Neuroradiology (HU), Medical Center - University of Freiburg, Freiburg, Germany; and Department of Neuropathology, University Heidelberg, Im Neuenheimer Feld 224 and German Cancer Consortium (DKTK), CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany (DC, DS).
authors.forename: Waseem
authors.initials: W
authors.lastname: Masalha
authors.affiliation: From the Department of Neurosurgery (DHH, WM, PF, JG, AW), Department of Pathology, Institute of Neuropathology (OS), Department of Neurosurgery, Epilepsy Center (MH), and Department of Neuroradiology (HU), Medical Center - University of Freiburg, Freiburg, Germany; and Department of Neuropathology, University Heidelberg, Im Neuenheimer Feld 224 and German Cancer Consortium (DKTK), CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany (DC, DS).
authors.forename: Pamela
authors.initials: P
authors.lastname: Franco
authors.affiliation: From the Department of Neurosurgery (DHH, WM, PF, JG, AW), Department of Pathology, Institute of Neuropathology (OS), Department of Neurosurgery, Epilepsy Center (MH), and Department of Neuroradiology (HU), Medical Center - University of Freiburg, Freiburg, Germany; and Department of Neuropathology, University Heidelberg, Im Neuenheimer Feld 224 and German Cancer Consortium (DKTK), CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany (DC, DS).
authors.forename: Jürgen
authors.initials: J
authors.lastname: Grauvogel
authors.affiliation: From the Department of Neurosurgery (DHH, WM, PF, JG, AW), Department of Pathology, Institute of Neuropathology (OS), Department of Neurosurgery, Epilepsy Center (MH), and Department of Neuroradiology (HU), Medical Center - University of Freiburg, Freiburg, Germany; and Department of Neuropathology, University Heidelberg, Im Neuenheimer Feld 224 and German Cancer Consortium (DKTK), CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany (DC, DS).
authors.forename: David
authors.initials: D
authors.lastname: Capper
authors.affiliation: From the Department of Neurosurgery (DHH, WM, PF, JG, AW), Department of Pathology, Institute of Neuropathology (OS), Department of Neurosurgery, Epilepsy Center (MH), and Department of Neuroradiology (HU), Medical Center - University of Freiburg, Freiburg, Germany; and Department of Neuropathology, University Heidelberg, Im Neuenheimer Feld 224 and German Cancer Consortium (DKTK), CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany (DC, DS).
authors.forename: Daniel
authors.initials: D
authors.lastname: Schrimpf
authors.affiliation: From the Department of Neurosurgery (DHH, WM, PF, JG, AW), Department of Pathology, Institute of Neuropathology (OS), Department of Neurosurgery, Epilepsy Center (MH), and Department of Neuroradiology (HU), Medical Center - University of Freiburg, Freiburg, Germany; and Department of Neuropathology, University Heidelberg, Im Neuenheimer Feld 224 and German Cancer Consortium (DKTK), CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany (DC, DS).
authors.forename: Horst
authors.initials: H
authors.lastname: Urbach
authors.affiliation: From the Department of Neurosurgery (DHH, WM, PF, JG, AW), Department of Pathology, Institute of Neuropathology (OS), Department of Neurosurgery, Epilepsy Center (MH), and Department of Neuroradiology (HU), Medical Center - University of Freiburg, Freiburg, Germany; and Department of Neuropathology, University Heidelberg, Im Neuenheimer Feld 224 and German Cancer Consortium (DKTK), CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany (DC, DS). astrid.weyerbrock@uniklinik-freiburg.de.
authors.forename: Astrid
authors.initials: A
authors.lastname: Weyerbrock
mesh_terms: D000328:Adult; D001324:Autoantigens / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016000:Cluster Analysis; D056915:DNA Copy Number Variations / Q000235:genetics; D004252:DNA Mutational Analysis; D015894:Genome, Human / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008745:Methylation; D018302:Neoplasms, Neuroepithelial / Q000235:genetics* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism
chemical_list: D001324:Autoantigens; D005904:Glial Fibrillary Acidic Protein; C099558:Ki antigen; D046988:Proteasome Endopeptidase Complex
keywords: Copy number changes; Dysembryoplastic neuroepithelial tumor (DNET); Epigenetic alteration; Illumina 450 K beadchip methylation array; Malignant DNET; Methylation.