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@ARTICLE{Federico:307434,
      author       = {A. Federico$^*$ and F. Schmitt-Hoffner$^*$ and A. Fonseca
                      and N. Geisemeyer$^*$ and K. Bruckner and M. Mauermann$^*$
                      and M. Sill$^*$ and D. Stichel and D. Sturm$^*$ and U.
                      Schüller and A. Tauziede-Espariat and P. Varlet and D.
                      Capper and Z. Abdullaev and D. Schrimpf$^*$ and F. Selt$^*$
                      and L. Williamson and A. M. Donson and M. Antonelli and E.
                      Miele and M. Snuderl and S. Brandner and M. Łastowska and
                      J. Van Der Lugt and J. Bunt and C. Kramm and A. Kolenova and
                      A. Raghunathan and Y. Wilson and L. Weintraub and J. R.
                      Hansford and S. Spiegl-Kreinecker and B. Aistleitner and L.
                      Baroni and M. Zapotocky and V. Ramaswamy and A.
                      Korshunov$^*$ and B. Jones$^*$ and M. Kjaersgaard and M. E.
                      Kranendonk and C. Haberler and R. J. Packer and N.
                      Jäger$^*$ and A. V. Deimling$^*$ and F. Sahm$^*$ and J.
                      Koster and K. Aldape and S. M. Pfister$^*$ and K. V. Hoff
                      and J. Gojo and M. Kool$^*$},
      title        = {{M}olecular and {C}linical {S}tratification of
                      {A}stroblastomas: {T}hree distinct {F}usion-{D}efined
                      {G}roups {I}nforming {R}isk-{A}dapted {T}reatment
                      {S}trategies.},
      journal      = {Neuro-Oncology},
      volume       = {nn},
      issn         = {1522-8517},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2025-03033},
      pages        = {nn},
      year         = {2025},
      note         = {#EA:B062#LA:B062# / epub},
      abstract     = {Astroblastomas are rare brain tumors predominantly
                      affecting children and young adults, for which molecular
                      subtypes and clinical management remain undefined.We
                      analyzed tumor samples, molecular profiles, and clinical
                      data from 200 patients, classified as 'Astroblastoma,
                      MN1-altered' under WHO criteria, using DNA methylation
                      profiling, DNA/RNA profiling/sequencing, and survival
                      analyses.DNA methylation analyses identified three groups:
                      Group A (n = 143, characterized by MN1::BEND2 fusions,
                      predominantly supratentorial location, with striking female
                      predominance and favorable survival); Group B (n = 37,
                      epigenetically and transcriptionally closely related to
                      Group A, but characterized by EWSR1::BEND2 fusions, with
                      spinal and infratentorial locations and poor prognosis); and
                      Group C (n = 20, epigenetically and transcriptionally
                      distinct, characterized by MN1::CXXC5 fusions, exclusively
                      supratentorially located, with favorable survival).
                      Progression-free and overall survival were significantly
                      shorter in Group B (5-year PFS $14\%;$ 10-year OS $54\%)$
                      compared to A (5-year PFS $47\%;$ 10-year OS $89\%)$ and C
                      (5-year PFS $75\%;$ 10-year OS $89\%).$ Radiotherapy
                      improved PFS in Group B (hazard ratio 0.25), while no clear
                      benefit was identified for Group A and C.Astroblastoma,
                      MN1-altered, comprises three molecularly and clinically
                      distinct groups, characterized by different fusion genes,
                      including those without MN1. These new insights, including
                      identification of potential predictive biomarkers like
                      14q/16q loss, provide a framework for development of
                      risk-stratified therapeutic approaches. Importantly, we
                      identified a molecularly defined high-risk group that
                      benefits from radiation therapy. Our findings redefine
                      Astroblastoma as a molecularly diverse tumor type, propose a
                      refined classification, support the development of
                      risk-adapted therapeutic strategies and provide a rational
                      standard of care.},
      keywords     = {EWSR1::BEND2 (Other) / MN1-altered (Other) / MN1::BEND2
                      (Other) / MN1::CXXC5 (Other) / Astroblastoma (Other) / gene
                      fusion (Other)},
      cin          = {B062 / HD01 / BE01 / B360 / B300},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)BE01-20160331 / I:(DE-He78)B360-20160331 /
                      I:(DE-He78)B300-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41429568},
      doi          = {10.1093/neuonc/noaf283},
      url          = {https://inrepo02.dkfz.de/record/307434},
}