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@ARTICLE{Krech:302003,
      author       = {M. Krech and A. Muench and D. Teichmann and P. Kuzman and
                      A. K. Suwala$^*$ and F. M. Ippen and M. Müther and K.
                      Weber$^*$ and K. Wenger-Alakmeh and J. Onken and P. Vajkoczy
                      and F. Behling and S.-A. May and G. Ntoulias and J. K.
                      Krauss and O. Atallah and M. Esmaeilzadeh and W. C. Mueller
                      and F. L. Heppner and H. Radbruch and C. Dittmayer and W.
                      Stenzel and A. Koch and D. Capper$^*$ and D. Kaul$^*$ and W.
                      Paulus and K. H. Plate$^*$ and J. P. Steinbach$^*$ and M.
                      Czabanka and R. Beschorner and A. von Deimling$^*$ and M.
                      Bockmayr and J. E. Neumann and S. Brandner and T. Krieger
                      and C. Hartmann and C. Thomas and L. Schweizer$^*$},
      title        = {{O}utcome-associated factors in a molecularly defined
                      cohort of central neurocytoma.},
      journal      = {Acta neuropathologica},
      volume       = {149},
      number       = {1},
      issn         = {0001-6322},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2025-01202},
      pages        = {61},
      year         = {2025},
      abstract     = {Central neurocytomas (CN) are intraventricular brain tumors
                      predominantly occurring in young adults. Although prognosis
                      is usually favorable, tumor recurrence is common,
                      particularly following subtotal resection (STR). Currently,
                      the risk of progression is evaluated using atypical features
                      and an elevated Ki67 proliferation index. However, these
                      markers lack consistent definitions, raising the need for
                      objective criteria. Genome-wide DNA methylation profiles
                      were examined in 136 tumors histologically classified as CN.
                      Clinical/histopathological characteristics were assessed in
                      93/90 cases, and whole-exome sequencing was conducted in 12
                      cases. Clinical and molecular characteristics were
                      integrated into a survival model to predict progression-free
                      survival (PFS). A diagnosis of CN was epigenetically
                      confirmed in 125 of 136 cases $(92\%).$ No DNA methylation
                      subgroups were identified, but global DNA hypomethylation
                      emerged as a hallmark feature of CN associated with higher
                      recurrence risk. Risk stratification based on histological
                      features of atypia and Ki67 proliferation index was not
                      reproducible across neuropathologists. Hypomethylation at
                      the FGFR3 locus, accompanied by increased FGFR3 protein
                      expression, was observed in $97\%$ of cases. Gross total
                      resection was associated with significantly improved PFS
                      compared to STR, while patients undergoing STR receiving
                      radiotherapy had a better outcome (p = 0.0001). Younger
                      patients were identified as having a higher risk of
                      recurrence (p = 0.026). Patient age and treatment strategy
                      were key factors associated with survival outcomes in this
                      cohort. These findings underscore the importance of closer
                      follow-up for younger patients and radiotherapy for STR
                      cases. Furthermore, FGFR3 represents a hallmark feature and
                      potential therapeutic target, warranting further
                      investigation.},
      keywords     = {Humans / Male / Female / Neurocytoma: genetics /
                      Neurocytoma: pathology / Adult / Young Adult / Brain
                      Neoplasms: genetics / Brain Neoplasms: pathology / DNA
                      Methylation / Middle Aged / Adolescent / Cohort Studies /
                      Neoplasm Recurrence, Local: genetics / Prognosis / DNA
                      methylation profiling (Other) / FGFR3 (Other) / Neurocytoma
                      (Other) / Progression-free survival (Other) / Radiotherapy
                      (Other)},
      cin          = {B300 / HD01 / FM01 / BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)FM01-20160331 / I:(DE-He78)BE01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40498174},
      doi          = {10.1007/s00401-025-02894-3},
      url          = {https://inrepo02.dkfz.de/record/302003},
}