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@ARTICLE{Okonechnikov:277922,
      author       = {K. Okonechnikov$^*$ and P. K. Joshi$^*$ and M. Sepp and K.
                      Leiss and I. Sarropoulos and F. Murat and M. Sill$^*$ and P.
                      Beck$^*$ and K. C. Chan$^*$ and A. Korshunov$^*$ and F.
                      Sahm$^*$ and M. Y. Deng$^*$ and D. Sturm$^*$ and J. DeSisto
                      and A. M. Donson and N. K. Foreman and A. L. Green and G.
                      Robinson and B. A. Orr and Q. Gao and E. Darrow and J. L.
                      Hadley and P. A. Northcott and J. Gojo$^*$ and D. Kawauchi
                      and V. Hovestadt and M. G. Filbin and A. von Deimling$^*$
                      and M. Zuckermann$^*$ and K. Pajtler$^*$ and M. Kool$^*$ and
                      D. Jones$^*$ and N. Jäger$^*$ and L. Kutscher$^*$ and H.
                      Kaessmann and S. Pfister$^*$},
      title        = {{M}apping pediatric brain tumors to their origins in the
                      developing cerebellum.},
      journal      = {Neuro-Oncology},
      volume       = {25},
      number       = {10},
      issn         = {1522-8517},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2023-01578},
      pages        = {1895-1909},
      year         = {2023},
      note         = {DKFZ-ZMBH Alliance / #EA:B062#EA:B430#LA:B062#LA:B430# /
                      2023 Oct 3;25(10):1895-1909},
      abstract     = {Distinguishing the cellular origins of childhood brain
                      tumors is key for understanding tumor initiation and
                      identifying lineage-restricted, tumor-specific therapeutic
                      targets. Previous strategies to map the cell-of-origin
                      typically involved comparing human tumors to murine
                      embryonal tissues, which is potentially limited due to
                      species-specific differences. The aim of this study was to
                      unravel the cellular origins of the three most common
                      pediatric brain tumors, ependymoma, pilocytic astrocytoma,
                      and medulloblastoma, using a developing human cerebellar
                      atlas.We used a single-nucleus atlas of the normal
                      developing human cerebellum consisting of 176,645 cells as a
                      reference for an in-depth comparison to 4,416 bulk and
                      single-cell transcriptome tumor datasets, using gene set
                      variation analysis, correlation, and single-cell matching
                      techniques.We find that the astroglial cerebellar lineage is
                      potentially the origin for posterior fossa ependymomas. We
                      propose that infratentorial pilocytic astrocytomas originate
                      from the oligodendrocyte lineage and MHC II genes are
                      specifically enriched in these tumors. We confirm that SHH
                      and Group 3/4 medulloblastomas originate from the granule
                      cell and unipolar brush cell lineages. Radiation-induced
                      gliomas stem from cerebellar glial lineages and demonstrate
                      distinct origins from the primary medulloblastoma. We
                      identify tumor genes that are expressed in the cerebellar
                      lineage of origin, and genes that are tumor specific; both
                      gene sets represent promising therapeutic targets for future
                      study.Based on our results, individual cells within a tumor
                      may resemble different cell types along a restricted
                      developmental lineage. Therefore, we suggest that tumors can
                      arise from multiple cellular states along the cerebellar
                      'lineage of origin'.},
      keywords     = {cerebellum (Other) / ependymoma (Other) / medulloblastoma
                      (Other) / pilocytic astrocytoma (Other) / radiation-induced
                      glioma (Other) / tumor origin (Other)},
      cin          = {B062 / HD01 / B430 / B300 / B360},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B430-20160331 / I:(DE-He78)B300-20160331 /
                      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:37534924},
      doi          = {10.1093/neuonc/noad124},
      url          = {https://inrepo02.dkfz.de/record/277922},
}