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1000 Titel
  • Transcriptomic and epigenetic dissection of spinal ependymoma (SP-EPN) identifies clinically relevant subtypes enriched for tumors with and without NF2 mutation
1000 Autor/in
  1. Neyazi, Sina |
  2. Yamazawa, Erika |
  3. Hack, Karoline |
  4. Tanaka, Shota |
  5. Nagae, Genta |
  6. Kresbach, Catena |
  7. Umeda, Takayoshi |
  8. Eckhardt, Alicia |
  9. Tatsuno, Kenji |
  10. Pohl, Lara |
  11. Hana, Taijun |
  12. Bockmayr, Michael |
  13. Kim, Phyo |
  14. Dorostkar, Mario M. |
  15. Takami, Toshihiro |
  16. Obrecht, Denise |
  17. Takai, Keisuke |
  18. Suwala, Abigail K. |
  19. Komori, Takashi |
  20. Godbole, Shweta |
  21. Wefers, Annika K. |
  22. Otani, Ryohei |
  23. Neumann, Julia E. |
  24. Higuchi, Fumi |
  25. Schweizer, Leonille |
  26. Nakanishi, Yuta |
  27. Monoranu, Camelia-Maria |
  28. Takami, Hirokazu |
  29. Engertsberger, Lara |
  30. Yamada, Keisuke |
  31. Ruf, Viktoria |
  32. Nomura, Masashi |
  33. Mohme, Theresa |
  34. Mukasa, Akitake |
  35. Herms, Jochen |
  36. Takayanagi, Shunsaku |
  37. Mynarek, Martin |
  38. Matsuura, Reiko |
  39. Lamszus, Katrin |
  40. Ishii, Kazuhiko |
  41. Kluwe, Lan |
  42. Imai, Hideaki |
  43. von Deimling, Andreas |
  44. Koike, Tsukasa |
  45. Benesch, Martin |
  46. Kushihara, Yoshihiro |
  47. Snuderl, Matija |
  48. Nambu, Shohei |
  49. Frank, Stephan |
  50. Omura, Takaki |
  51. Hagel, Christian |
  52. Kugasawa, Kazuha |
  53. Mautner, Viktor F. |
  54. Ichimura, Koichi |
  55. Rutkowski, Stefan |
  56. Aburatani, Hiroyuki |
  57. Saito, Nobuhito |
  58. Schüller, Ulrich |
1000 Verlag Springer Berlin Heidelberg
1000 Erscheinungsjahr 2024
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2024-01-24
1000 Erschienen in
1000 Quellenangabe
  • 147(1):22
1000 Copyrightjahr
  • 2024
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00401-023-02668-9 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10808175/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • <jats:title>Abstract</jats:title><jats:p>Ependymomas encompass multiple clinically relevant tumor types based on localization and molecular profiles. Tumors of the methylation class “spinal ependymoma” (SP-EPN) represent the most common intramedullary neoplasms in children and adults. However, their developmental origin is ill-defined, molecular data are scarce, and the potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and <jats:italic>NF2</jats:italic> mutations, but neither types and frequency of these alterations nor their clinical relevance have been described in a large, epigenetically defined series. Transcriptomic (<jats:italic>n</jats:italic> = 72), epigenetic (<jats:italic>n</jats:italic> = 225), genetic (<jats:italic>n</jats:italic> = 134), and clinical data (<jats:italic>n</jats:italic> = 112) were integrated for a detailed molecular overview on SP-EPN. Additionally, we mapped SP-EPN transcriptomes to developmental atlases of the developing and adult spinal cord to uncover potential developmental origins of these tumors. The integration of transcriptomic ependymoma data with single-cell atlases of the spinal cord revealed that SP-EPN display the highest similarities to mature adult ependymal cells. Unsupervised hierarchical clustering of transcriptomic data together with integrated analysis of methylation profiles identified two molecular SP-EPN subtypes. Subtype A tumors primarily carried previously known germline or sporadic <jats:italic>NF2</jats:italic> mutations together with 22q loss (bi-allelic <jats:italic>NF2</jats:italic> loss), resulting in decreased <jats:italic>NF2</jats:italic> expression. Furthermore, they more often presented as multilocular disease and demonstrated a significantly reduced progression-free survival as compared to SP-EP subtype B. In contrast, subtype B predominantly contained samples without <jats:italic>NF2</jats:italic> mutation detected in sequencing together with 22q loss (monoallelic <jats:italic>NF2</jats:italic> loss). These tumors showed regular <jats:italic>NF2</jats:italic> expression but more extensive global copy number alterations. Based on integrated molecular profiling of a large multi-center cohort, we identified two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities.</jats:p>
1000 Sacherschließung
lokal Mutation [MeSH]
lokal Classification
lokal Adult [MeSH]
lokal Humans [MeSH]
lokal Ependymoma [MeSH]
lokal Epigenesis, Genetic [MeSH]
lokal Original Paper
lokal Ependymoma
lokal Transcriptome [MeSH]
lokal DNA methylation
lokal Transcriptomics
lokal Gene Expression Profiling [MeSH]
lokal Child [MeSH]
lokal Spinal Cord Neoplasms [MeSH]
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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  1. Deutsche Forschungsgemeinschaft |
  2. Fördergemeinschaft Kinderkrebs-Zentrum Hamburg |
  3. Universitätsklinikum Hamburg-Eppendorf (UKE) |
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