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@ARTICLE{Donson:276332,
      author       = {A. M. Donson and K. C. Bertrand and K. A. Riemondy and D.
                      Gao and Y. Zhuang and B. Sanford and G. A. Norris and R. J.
                      Chapman and R. Fu and N. Willard and A. M. Griesinger and G.
                      R. de Sousa and V. Amani and E. Grimaldo and T. C. Hankinson
                      and F. Booker and M. Sill$^*$ and R. G. Grundy and K.
                      Pajtler$^*$ and D. W. Ellison and N. K. Foreman and T. A.
                      Ritzmann},
      title        = {{S}ignificant increase of high-risk chromosome 1q gain and
                      6q loss at recurrence in posterior fossa group {A}
                      ependymoma: a multicenter study.},
      journal      = {Neuro-Oncology},
      volume       = {25},
      number       = {10},
      issn         = {1522-8517},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2023-01062},
      pages        = {1854-1867},
      year         = {2023},
      note         = {2023 Oct 3;25(10):1854-1867},
      abstract     = {Ependymoma (EPN) posterior fossa group A (PFA) has the
                      highest rate of recurrence and the worst prognosis of all
                      EPN molecular groups. At relapse, it is typically incurable
                      even with re-resection and re-irradiation. The biology of
                      recurrent PFA remains largely unknown, however, the
                      increasing use of surgery at first recurrence has now
                      provided access to clinical samples to facilitate a better
                      understanding of this.In this large longitudinal
                      international multicenter study, we examined matched samples
                      of primary and recurrent disease from PFA patients to
                      investigate the biology of recurrence.DNA methylome derived
                      copy number variants (CNVs) revealed large scale chromosome
                      gains and losses at recurrence. CNV changes were dominated
                      by chromosome 1q gain and/or 6q loss, both previously
                      identified as high-risk factors in PFA, which were present
                      in $23\%$ at presentation but increased to $61\%$ at 1 st
                      recurrence. Multivariate survival analyses of this cohort
                      showed that cases with 1q gain or 6q loss at 1 st recurrence
                      were significantly more likely to recur again.
                      Predisposition to 1q+/6q- CNV changes at recurrence
                      correlated with hypomethylation of
                      heterochromatin-associated DNA at presentation. Cellular and
                      molecular analyses revealed that 1q+/6q- PFA had
                      significantly higher proportions of proliferative
                      neuroepithelial undifferentiated progenitors and decreased
                      differentiated neoplastic subpopulations.This study provides
                      clinically and preclinically-actionable insights into the
                      biology of PFA recurrence. The hypomethylation
                      predisposition signature in PFA is a potential
                      risk-classifier for trial stratification. We show that the
                      cellular heterogeneity of PFAs evolves largely because of
                      genetic evolution of neoplastic cells.},
      keywords     = {chromosomal instability (Other) / ependymoma (Other) /
                      prognosis (Other) / recurrence (Other)},
      cin          = {B062 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37246777},
      doi          = {10.1093/neuonc/noad096},
      url          = {https://inrepo02.dkfz.de/record/276332},
}