Malignant Transformation of a Dysembryoplastic Neuroepithelial Tumor (DNET) Characterized by Genome-Wide Methylation Analysis

J Neuropathol Exp Neurol. 2016 Apr;75(4):358-65. doi: 10.1093/jnen/nlw007. Epub 2016 Feb 27.

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.

Keywords: Copy number changes; Dysembryoplastic neuroepithelial tumor (DNET); Epigenetic alteration; Illumina 450 K beadchip methylation array; Malignant DNET; Methylation..

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantigens / metabolism
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Transformation, Neoplastic / genetics
  • Cluster Analysis
  • DNA Copy Number Variations / genetics
  • DNA Mutational Analysis
  • Genome, Human / genetics
  • Glial Fibrillary Acidic Protein
  • Glioblastoma / genetics*
  • Glioblastoma / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Methylation
  • Neoplasms, Neuroepithelial / genetics*
  • Neoplasms, Neuroepithelial / pathology
  • Proteasome Endopeptidase Complex / metabolism

Substances

  • Autoantigens
  • Glial Fibrillary Acidic Protein
  • Ki antigen
  • Proteasome Endopeptidase Complex