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@ARTICLE{Goschzik:306599,
      author       = {T. Goschzik and M. Yuan and E. Pfaff$^*$ and M. E. B.
                      Müller and M. Mynarek and E. Dörner and D. T. W. Jones$^*$
                      and S. M. Pfister$^*$ and S. Rutkowski and T. Pietsch},
      title        = {{R}ecurrent genetic alterations in epigenetically defined
                      pineoblastoma subtypes.},
      journal      = {Acta Neuropathologica Communications},
      volume       = {13},
      number       = {1},
      issn         = {2051-5960},
      address      = {London},
      publisher    = {Biomed Central},
      reportid     = {DKFZ-2025-02638},
      pages        = {241},
      year         = {2025},
      abstract     = {Previous studies have revealed four distinct epigenetic
                      consensus pineoblastoma (PB) subtypes. The aim of this study
                      was to confirm and further extend their respective genetic
                      underpinnings. Cytogenetics of 83 PB were analyzed by
                      high-resolution genome-wide molecular inversion probe
                      analysis and methylation profiling. Seventy-nine cases were
                      screened for mutations by next-generation DNA panel
                      sequencing and for 25 samples mRNA expression was analyzed
                      using NanoString. Additionally, 24 further pineal
                      parenchymal tumors were analyzed. Clinical data of 63
                      patients was available. Our cohort consisted of 48
                      PB-miRNA1, 19 PB-miRNA2, 8 PB-MYC/FOXR2, and 8 PB-RB1 cases.
                      PB-miRNA subtype tumors had characteristic alterations in
                      microRNA-processing genes; DICER1 mutations (n = 19/64) and
                      homozygous deletions of the DROSHA locus (n = 18/67) were
                      most abundant, followed by DROSHA mutations (n = 12/64).
                      Most frequent cytogenetic aberrations in PB-miRNA cases were
                      chromosome 7 gains (n = 31/67) and chromosome 14 losses (n =
                      26/67, including 5 cases with copy-neutral LOH). The latter
                      were significantly associated with DICER1 mutations (p <
                      0.001). OTX2 gain represented the most frequent alteration
                      that occurred in 37/83 PB of all subtypes. In the PB-miRNA
                      subtypes we identified cases with polyploid cytogenetics (n
                      = 16/67). In contrast to previous publications, we did not
                      find a difference in survival for the PB-miRNA subtypes,
                      whereas PB-MYC/FOXR2 and PB-RB1 in infants showed a worse
                      outcome. Epigenetically defined PB subtypes are
                      characterized by distinct genetic events. Frequent gains of
                      the oncogene OTX2 indicate a role in the pathogenesis of PB
                      independent of its subtype.},
      keywords     = {Humans / Pinealoma: genetics / Pinealoma: classification /
                      Pinealoma: pathology / Female / Male / Brain Neoplasms:
                      genetics / Brain Neoplasms: classification / Brain
                      Neoplasms: pathology / Child / Child, Preschool / Pineal
                      Gland: pathology / Adult / Ribonuclease III: genetics /
                      Adolescent / Epigenesis, Genetic: genetics / MicroRNAs:
                      genetics / Mutation: genetics / Young Adult / Middle Aged /
                      Infant / DEAD-box RNA Helicases: genetics / DNA Methylation
                      / Otx Transcription Factors: genetics / DICER1 (Other) /
                      DROSHA (Other) / Epigenetic subtypes (Other) / PPTID (Other)
                      / Pineoblastoma (Other) / Ribonuclease III (NLM Chemicals) /
                      MicroRNAs (NLM Chemicals) / DICER1 protein, human (NLM
                      Chemicals) / DEAD-box RNA Helicases (NLM Chemicals) / Otx
                      Transcription Factors (NLM Chemicals)},
      cin          = {B360 / B062 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B360-20160331 / 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:41291966},
      pmc          = {pmc:PMC12648887},
      doi          = {10.1186/s40478-025-02140-7},
      url          = {https://inrepo02.dkfz.de/record/306599},
}