% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Tonn:212544,
      author       = {S. Tonn and A. Korshunov$^*$ and D. Obrecht and M. Sill$^*$
                      and M. Spohn and K. von Hoff and T. Milde$^*$ and T. Pietsch
                      and T. Goschzik and B. Bison and B.-O. Juhnke and N. Struve
                      and D. Sturm$^*$ and F. Sahm$^*$ and M. Bockmayr and C.
                      Friedrich and A. O. von Bueren and N. U. Gerber and M.
                      Benesch and D. Jones$^*$ and M. Kool$^*$ and A. K. Wefers
                      and U. Schüller and S. Pfister$^*$ and S. Rutkowski and M.
                      Mynarek},
      title        = {{R}isk prediction in early childhood {SHH} medulloblastoma
                      treated with radiation-avoiding chemotherapy: {E}vidence for
                      more than two subgroups.},
      journal      = {Neuro-Oncology},
      volume       = {25},
      number       = {8},
      issn         = {1522-8517},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2023-00229},
      pages        = {1518-1529},
      year         = {2023},
      note         = {2023 Aug 3;25(8):1518-1529},
      abstract     = {The prognostic impact of clinical risk factors and DNA
                      methylation patterns in sonic hedgehog (SHH)-activated early
                      childhood desmoplastic/nodular medulloblastoma (DMB) or
                      medulloblastoma with extensive nodularity (MBEN) were
                      evaluated to better identify patients at risk for
                      relapse.Hundred-forty-four patients with DMB (n=99) or MBEN
                      (n=45) aged <5 years and treated with radiation-sparing
                      approaches, including intraventricular methotrexate in 132
                      patients, were evaluated.Patients with DMB had less
                      favorable 5-year progression-free survival than MBEN
                      (5y-PFS, $71\%$ [DMB] vs $93\%$ [MBEN]). Patients' age >3
                      years was associated with more unfavorable 5y-PFS $(47\%$
                      [>3 years] vs $85\%$ [<1 year] vs $84\%$ [1-3 years]). DNA
                      methylation profiles available (n=78) were reclassified
                      according to the 2021 WHO classification into SHH-1 (n=39),
                      SHH-2 (n=38), and SHH-3 (n=1). Hierarchical clustering
                      delineated two subgroups among SHH-2: SHH-2a (n=19) and
                      SHH-2b (n=19). Patients with SHH-2b medulloblastoma were
                      older, predominantly displayed DMB histology, and were more
                      often located in the cerebellar hemispheres. Chromosome 9q
                      losses were more frequent in SHH-2b, while few chromosomal
                      alterations were observed in SHH-2a. SHH-2b medulloblastoma
                      carried a significantly increased relapse risk (5y-PFS:
                      $58\%$ [SHH-2b] vs $83\%$ [SHH-1] vs $95\%$ [SHH-2a]).
                      Subclassification of SHH-2 with key clinical and cytogenetic
                      characteristics was confirmed using two independent cohorts
                      (total n=188). Gene mutation analysis revealed a correlation
                      of SHH-2a with SMO mutations.These data suggest further
                      heterogeneity within early childhood SHH-DMB/MBEN: SHH-2
                      splits into a very low-risk group SHH-2a enriched for MBEN
                      histology and SMO mutations, and SHH-2b comprising older DMB
                      patients with higher risk of relapse.},
      keywords     = {DNA methylation profiling (Other) / Medulloblastoma (Other)
                      / Risk prediction (Other) / Sonic hedgehog-activated
                      (Other)},
      cin          = {B300 / HD01 / B062 / B310 / B360},
      ddc          = {610},
      cid          = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)B310-20160331 /
                      I:(DE-He78)B360-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36715306},
      doi          = {10.1093/neuonc/noad027},
      url          = {https://inrepo02.dkfz.de/record/212544},
}