Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1

  1. Suwala, Abigail K.
  2. Stichel, Damian
  3. Schrimpf, Daniel
  4. Maas, Sybren L. N.
  5. Sill, Martin
  6. Dohmen, Hildegard
  7. Banan, Rouzbeh
  8. Reinhardt, Annekathrin
  9. Sievers, Philipp
  10. Hinz, Felix
  11. Blattner-Johnson, Mirjam
  12. Hartmann, Christian
  13. Schweizer, Leonille
  14. Boldt, Henning B.
  15. Kristensen, Bjarne Winther
  16. Schittenhelm, Jens
  17. Wood, Matthew D.
  18. Chotard, Guillaume
  19. Bjergvig, Rolf
  20. Das, Anirban
  21. Tabori, Uri
  22. Hasselblatt, Martin
  23. Korshunov, Andrey
  24. Abdullaev, Zied
  25. Quezado, Martha
  26. Aldape, Kenneth
  27. Harter, Patrick N.
  28. Snuderl, Matija
  29. Hench, Jürgen
  30. Frank, Stephan
  31. Acker, Till
  32. Brandner, Sebastian
  33. Winkler, Frank
  34. Wesseling, Pieter
  35. Pfister, Stefan M.
  36. Reuss, David E.
  37. Wick, Wolfgang
  38. von Deimling, Andreas
  39. Jones, David T. W.
  40. Sahm, Felix ORCID logo

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1000 Titel
  • Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1
1000 Autor/in
  1. Suwala, Abigail K. |
  2. Stichel, Damian |
  3. Schrimpf, Daniel |
  4. Maas, Sybren L. N. |
  5. Sill, Martin |
  6. Dohmen, Hildegard |
  7. Banan, Rouzbeh |
  8. Reinhardt, Annekathrin |
  9. Sievers, Philipp |
  10. Hinz, Felix |
  11. Blattner-Johnson, Mirjam |
  12. Hartmann, Christian |
  13. Schweizer, Leonille |
  14. Boldt, Henning B. |
  15. Kristensen, Bjarne Winther |
  16. Schittenhelm, Jens |
  17. Wood, Matthew D. |
  18. Chotard, Guillaume |
  19. Bjergvig, Rolf |
  20. Das, Anirban |
  21. Tabori, Uri |
  22. Hasselblatt, Martin |
  23. Korshunov, Andrey |
  24. Abdullaev, Zied |
  25. Quezado, Martha |
  26. Aldape, Kenneth |
  27. Harter, Patrick N. |
  28. Snuderl, Matija |
  29. Hench, Jürgen |
  30. Frank, Stephan |
  31. Acker, Till |
  32. Brandner, Sebastian |
  33. Winkler, Frank |
  34. Wesseling, Pieter |
  35. Pfister, Stefan M. |
  36. Reuss, David E. |
  37. Wick, Wolfgang |
  38. von Deimling, Andreas |
  39. Jones, David T. W. |
  40. Sahm, Felix |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-04-19
1000 Erschienen in
1000 Quellenangabe
  • 142(1):179-189
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00401-021-02302-6 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217054/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.
1000 Sacherschließung
lokal Ubiquitin-Protein Ligases/genetics [MeSH]
lokal Glial Fibrillary Acidic Protein/biosynthesis [MeSH]
lokal Glioblastoma/pathology [MeSH]
lokal Cohort Studies [MeSH]
lokal Neuroectodermal Tumors, Primitive/genetics [MeSH]
lokal Male [MeSH]
lokal DNA methylation
lokal Retinoblastoma Binding Proteins/genetics [MeSH]
lokal Glioblastoma/genetics [MeSH]
lokal Gene Deletion [MeSH]
lokal Female [MeSH]
lokal Neuroectodermal Tumors, Primitive/pathology [MeSH]
lokal Phenotype
lokal Brain Neoplasms/genetics [MeSH]
lokal GBM
lokal Classification
lokal Humans [MeSH]
lokal PTEN Phosphohydrolase/genetics [MeSH]
lokal Chromosomes, Human, Pair 7/genetics [MeSH]
lokal Middle Aged [MeSH]
lokal Glial Fibrillary Acidic Protein/genetics [MeSH]
lokal PNET
lokal Tumor Suppressor Protein p53/genetics [MeSH]
lokal Cyclin-Dependent Kinase Inhibitor p16/genetics [MeSH]
lokal DNA Copy Number Variations [MeSH]
lokal DNA Methylation [MeSH]
lokal Plasticity
lokal Original Paper
lokal Chromosomes, Human, Pair 1/genetics [MeSH]
lokal Brain Neoplasms/pathology [MeSH]
1000 Liste der Beteiligten
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1000 Erstellt am 2023-05-11T10:48:10.995+0200
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1000 Zuletzt bearbeitet Sat Oct 21 03:56:44 CEST 2023
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