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@ARTICLE{Neyazi:267352,
      author       = {Neyazi, Sina and Yamazawa, Erika and Hack, Karoline and
                      Tanaka, Shota and Nagae, Genta and Kresbach, Catena and
                      Umeda, Takayoshi and Eckhardt, Alicia and Tatsuno, Kenji and
                      Pohl, Lara and Hana, Taijun and Bockmayr, Michael and Kim,
                      Phyo and Dorostkar, Mario M and Takami, Toshihiro and
                      Obrecht, Denise and Takai, Keisuke and Suwala, Abigail K and
                      Komori, Takashi and Godbole, Shweta and Wefers, Annika K and
                      Otani, Ryohei and Neumann, Julia E and Higuchi, Fumi and
                      Schweizer, Leonille and Nakanishi, Yuta and Monoranu,
                      Camelia-Maria and Takami, Hirokazu and Engertsberger, Lara
                      and Yamada, Keisuke and Ruf, Viktoria and Nomura, Masashi
                      and Mohme, Theresa and Mukasa, Akitake and Herms, Jochen and
                      Takayanagi, Shunsaku and Mynarek, Martin and Matsuura, Reiko
                      and Lamszus, Katrin and Ishii, Kazuhiko and Kluwe, Lan and
                      Imai, Hideaki and von Deimling, Andreas and Koike, Tsukasa
                      and Benesch, Martin and Kushihara, Yoshihiro and Snuderl,
                      Matija and Nambu, Shohei and Frank, Stephan and Omura,
                      Takaki and Hagel, Christian and Kugasawa, Kazuha and
                      Mautner, Viktor F and Ichimura, Koichi and Rutkowski, Stefan
                      and Aburatani, Hiroyuki and Saito, Nobuhito and Schüller,
                      Ulrich},
      title        = {{T}ranscriptomic and epigenetic dissection of spinal
                      ependymoma ({SP}-{EPN}) identifies clinically relevant
                      subtypes enriched for tumors with and without {NF}2
                      mutation.},
      journal      = {Acta neuropathologica},
      volume       = {147},
      number       = {1},
      issn         = {0001-6322},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DZNE-2024-00116},
      pages        = {22},
      year         = {2024},
      abstract     = {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 NF2 mutations, but neither types and
                      frequency of these alterations nor their clinical relevance
                      have been described in a large, epigenetically defined
                      series. Transcriptomic (n = 72), epigenetic (n = 225),
                      genetic (n = 134), and clinical data (n = 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 NF2 mutations together with 22q
                      loss (bi-allelic NF2 loss), resulting in decreased NF2
                      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 NF2 mutation detected in sequencing together
                      with 22q loss (monoallelic NF2 loss). These tumors showed
                      regular NF2 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.},
      keywords     = {Adult / Child / Humans / Transcriptome / Gene Expression
                      Profiling / Ependymoma / Spinal Cord Neoplasms / Mutation /
                      Epigenesis, Genetic / Classification (Other) / DNA
                      methylation (Other) / Ependymoma (Other) / NF2-related
                      schwannomatosis (Other) / Transcriptomics (Other)},
      cin          = {AG Herms},
      ddc          = {610},
      cid          = {I:(DE-2719)1110001},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38265489},
      pmc          = {pmc:PMC10808175},
      doi          = {10.1007/s00401-023-02668-9},
      url          = {https://pub.dzne.de/record/267352},
}