Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors

  1. Sievers, Philipp
  2. Henneken, Sophie C.
  3. Blume, Christina
  4. Sill, Martin
  5. Schrimpf, Daniel
  6. Stichel, Damian
  7. Okonechnikov, Konstantin
  8. Reuss, David E.
  9. Benzel, Julia
  10. Maaß, Kendra K.
  11. Kool, Marcel
  12. Sturm, Dominik
  13. Zheng, Tuyu
  14. Ghasemi, David R.
  15. Kohlhof-Meinecke, Patricia
  16. Cruz, Ofelia
  17. Suñol, Mariona
  18. Lavarino, Cinzia
  19. Ruf, Viktoria
  20. Boldt, Henning B.
  21. Pagès, Mélanie
  22. Pouget, Celso
  23. Schweizer, Leonille
  24. Kranendonk, Mariëtte E. G.
  25. Akhtar, Noreen
  26. Bunkowski, Stephanie
  27. Stadelmann , Christine
  28. Schüller, Ulrich
  29. Mueller, Wolf C.
  30. Dohmen, Hildegard
  31. Acker, Till
  32. Harter, Patrick N.
  33. Mawrin, Christian
  34. Beschorner, Rudi
  35. Brandner, Sebastian
  36. Snuderl, Matija
  37. Abdullaev, Zied
  38. Aldape, Kenneth
  39. Gilbert, Mark R.
  40. Armstrong, Terri S.
  41. Ellison, David W.
  42. Capper, David
  43. Ichimura, Koichi
  44. Reifenberger, Guido
  45. Grundy, Richard G.
  46. Jabado, Nada
  47. Krskova, Lenka
  48. Zapotocky, Michal
  49. Vicha, Ales
  50. Varlet, Pascale
  51. Wesseling, Pieter
  52. Rutkowski, Stefan
  53. Korshunov, Andrey
  54. Wick, Wolfgang
  55. Pfister, Stefan M.
  56. Jones, David T. W.
  57. von Deimling, Andreas
  58. Pajtler, Kristian W.
  59. Sahm, Felix ORCID logo

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1000 Titel
  • Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors
1000 Autor/in
  1. Sievers, Philipp |
  2. Henneken, Sophie C. |
  3. Blume, Christina |
  4. Sill, Martin |
  5. Schrimpf, Daniel |
  6. Stichel, Damian |
  7. Okonechnikov, Konstantin |
  8. Reuss, David E. |
  9. Benzel, Julia |
  10. Maaß, Kendra K. |
  11. Kool, Marcel |
  12. Sturm, Dominik |
  13. Zheng, Tuyu |
  14. Ghasemi, David R. |
  15. Kohlhof-Meinecke, Patricia |
  16. Cruz, Ofelia |
  17. Suñol, Mariona |
  18. Lavarino, Cinzia |
  19. Ruf, Viktoria |
  20. Boldt, Henning B. |
  21. Pagès, Mélanie |
  22. Pouget, Celso |
  23. Schweizer, Leonille |
  24. Kranendonk, Mariëtte E. G. |
  25. Akhtar, Noreen |
  26. Bunkowski, Stephanie |
  27. Stadelmann , Christine |
  28. Schüller, Ulrich |
  29. Mueller, Wolf C. |
  30. Dohmen, Hildegard |
  31. Acker, Till |
  32. Harter, Patrick N. |
  33. Mawrin, Christian |
  34. Beschorner, Rudi |
  35. Brandner, Sebastian |
  36. Snuderl, Matija |
  37. Abdullaev, Zied |
  38. Aldape, Kenneth |
  39. Gilbert, Mark R. |
  40. Armstrong, Terri S. |
  41. Ellison, David W. |
  42. Capper, David |
  43. Ichimura, Koichi |
  44. Reifenberger, Guido |
  45. Grundy, Richard G. |
  46. Jabado, Nada |
  47. Krskova, Lenka |
  48. Zapotocky, Michal |
  49. Vicha, Ales |
  50. Varlet, Pascale |
  51. Wesseling, Pieter |
  52. Rutkowski, Stefan |
  53. Korshunov, Andrey |
  54. Wick, Wolfgang |
  55. Pfister, Stefan M. |
  56. Jones, David T. W. |
  57. von Deimling, Andreas |
  58. Pajtler, Kristian W. |
  59. Sahm, Felix |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-08-05
1000 Erschienen in
1000 Quellenangabe
  • 142(5):827-839
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00401-021-02356-6 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500895/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Ependymomas encompass a heterogeneous group of central nervous system (CNS) neoplasms that occur along the entire neuroaxis. In recent years, extensive (epi-)genomic profiling efforts have identified several molecular groups of ependymoma that are characterized by distinct molecular alterations and/or patterns. Based on unsupervised visualization of a large cohort of genome-wide DNA methylation data, we identified a highly distinct group of pediatric-type tumors (n = 40) forming a cluster separate from all established CNS tumor types, of which a high proportion were histopathologically diagnosed as ependymoma. RNA sequencing revealed recurrent fusions involving the pleomorphic adenoma gene-like 1 (PLAGL1) gene in 19 of 20 of the samples analyzed, with the most common fusion being EWSR1:PLAGL1 (n = 13). Five tumors showed a PLAGL1:FOXO1 fusion and one a PLAGL1:EP300 fusion. High transcript levels of PLAGL1 were noted in these tumors, with concurrent overexpression of the imprinted genes H19 and IGF2, which are regulated by PLAGL1. Histopathological review of cases with sufficient material (n = 16) demonstrated a broad morphological spectrum of tumors with predominant ependymoma-like features. Immunohistochemically, tumors were GFAP positive and OLIG2- and SOX10 negative. In 3/16 of the cases, a dot-like positivity for EMA was detected. All tumors in our series were located in the supratentorial compartment. Median age of the patients at the time of diagnosis was 6.2 years. Median progression-free survival was 35 months (for 11 patients with data available). In summary, our findings suggest the existence of a novel group of supratentorial neuroepithelial tumors that are characterized by recurrent PLAGL1 fusions and enriched for pediatric patients.
1000 Sacherschließung
lokal
lokal Female [MeSH]
lokal Tumor Suppressor Proteins/genetics [MeSH]
lokal Cell Cycle Proteins/genetics [MeSH]
lokal Ependymoma/genetics [MeSH]
lokal Neuroepithelial tumor
lokal Transcription Factors/genetics [MeSH]
lokal Humans [MeSH]
lokal Oncogene Fusion [MeSH]
lokal Supratentorial
lokal Male [MeSH]
lokal Gene fusion
lokal Original Paper
lokal Supratentorial Neoplasms/genetics [MeSH]
lokal Child [MeSH]
1000 Liste der Beteiligten
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