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Distribution of EGFR amplification, combined chromosome 7 gain and chromosome 10 loss, and TERT promoter mutation in brain tumors and their potential for the reclassification of IDHwt astrocytoma to glioblastoma.

  • Stichel D Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Ebrahimi A Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Reuss D Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Schrimpf D Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Ono T Department of Neurosurgery, Akita University Graduate School of Medicine, Akita, Japan.
  • Shirahata M Department of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Hidaka, Japan.
  • Reifenberger G Department of Neuropathology, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
  • Weller M Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
  • Hänggi D Department of Neurosurgery, University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany.
  • Wick W Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
  • Herold-Mende C Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany.
  • Westphal M Department of Neurosurgery, University Hamburg-Eppendorf, Martinistr. 52, 20251, Hamburg, Germany.
  • Brandner S Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London, UK.
  • Pfister SM Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
  • Capper D Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Sahm F Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • von Deimling A Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. andreas.vondeimling@med.uni-heidelberg.de.
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  • 2018-09-07
Published in:
  • Acta neuropathologica. - 2018
7+/10q−
7+/10−
Astrocytoma
Chromosome 10 loss
Chromosome 7 gain
EGFR amplification
Glioblastoma
Pleomorphic xanthoastrocytoma
TERT promoter mutation
Adult
Aged
Astrocytoma
Brain
Brain Neoplasms
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 7
Cohort Studies
ErbB Receptors
Female
Glioblastoma
Humans
Isocitrate Dehydrogenase
Male
Middle Aged
Mutation
English EGFR amplification (EGFRamp), the combination of gain of chromosome 7 and loss of chromosome 10 (7+/10-), and TERT promoter mutation (pTERTmut) are alterations frequently observed in adult IDH-wild-type (IDHwt) glioblastoma (GBM). In the absence of endothelial proliferation and/or necrosis, these alterations currently are considered to serve as a surrogate for upgrading IDHwt diffuse or anaplastic astrocytoma to GBM. Here, we set out to determine the distribution of EGFRamp, 7+/10-, and pTERTmut by analyzing high-resolution copy-number profiles and next-generation sequencing data of primary brain tumors. In addition, we addressed the question whether combinations of partial gains on chromosome 7 and partial losses on chromosome 10 exhibited a diagnostic and prognostic value similar to that of complete 7+/10-. Several such combinations proved relevant and were combined as the 7/10 signature. Our results demonstrate that EGFRamp and the 7/10 signature are closely associated with IDHwt GBM. In contrast, pTERTmut is less specific for IDHwt GBM. We conclude that, in the absence of endothelial proliferation and/or necrosis, the detection of EGFRamp is a very strong surrogate marker for the diagnosis of GBM in IDHwt diffuse astrocytic tumors. The 7/10 signature is also a strong surrogate marker. However, care should be taken to exclude pleomorphic xanthoastrocytoma. pTERTmut is less restricted to this entity and needs companion analysis by other molecular markers to serve as a surrogate for diagnosing IDHwt GBM. A combination of any two of EGFRamp, the 7/10 signature and pTERTmut, is highly specific for IDHwt GBM and the combination of all three alterations is frequent and exclusively seen in IDHwt GBM.
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  • English
Open access status
green
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https://folia.unifr.ch/global/documents/128331
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