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@ARTICLE{Kats:294744,
      author       = {I. Kats$^*$ and M. Simovic-Lorenz$^*$ and H. Schreiber$^*$
                      and P. Sant$^*$ and J.-P. Mallm$^*$ and V. Körber and A.
                      Li$^*$ and P. Velmurugan$^*$ and S. Heuer$^*$ and L.
                      Kües$^*$ and F. Devens$^*$ and M. Sill$^*$ and M.
                      Jugold$^*$ and M. Moustafa$^*$ and A. Abdollahi$^*$ and F.
                      Winkler$^*$ and A. Korshunov$^*$ and S. Pfister$^*$ and O.
                      Stegle$^*$ and A. Ernst$^*$},
      title        = {{S}patio-temporal transcriptomics of chromothriptic
                      {SHH}-medulloblastoma identifies multiple genetic clones
                      that resist treatment and drive relapse.},
      journal      = {Nature Communications},
      volume       = {15},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Nature Publishing Group UK},
      reportid     = {DKFZ-2024-02459},
      pages        = {10370},
      year         = {2024},
      note         = {#EA:B260#LA:B420#LA:B420#},
      abstract     = {Paediatric medulloblastomas with chromothripsis are
                      characterised by high genomic instability and are among the
                      tumours with the worst prognosis. However, the molecular
                      makeup and the determinants of the aggressiveness of
                      chromothriptic medulloblastoma are not well understood.
                      Here, we apply spatial transcriptomics to profile a cohort
                      of 13 chromothriptic and non-chromothriptic medulloblastomas
                      from the same molecular subgroup. Our data reveal a higher
                      extent of spatial intra-tumour heterogeneity in
                      chromothriptic medulloblastomas compared to
                      non-chromothripictic tumours, which is associated with
                      increased proliferation and stemness, but lower immune
                      infiltration and differentiation. Spatial mapping of genetic
                      subclones of the same tumour identify a regionally distinct
                      architecture and clone-specific phenotypic features, with
                      distinct degrees of differentiation, proliferation and
                      immune infiltration between clones. We conduct temporal
                      profiling of 11 samples from patient-derived xenografts from
                      a patient with chromothriptic medulloblastoma, covering the
                      transition from the minimal residual disease stage to
                      treatment-resistant regrown tumours. In chromothriptic
                      medulloblastoma, an ecosystem of cells from multiple genetic
                      clones resist treatment and lead to relapse. Finally, we
                      identify tumour microtubes in chromothriptic
                      medulloblastoma, calling for exploration of cell network
                      communication as a putative target.},
      keywords     = {Medulloblastoma: genetics / Medulloblastoma: pathology /
                      Medulloblastoma: metabolism / Humans / Cerebellar Neoplasms:
                      genetics / Cerebellar Neoplasms: pathology / Cerebellar
                      Neoplasms: metabolism / Animals / Transcriptome / Hedgehog
                      Proteins: metabolism / Hedgehog Proteins: genetics /
                      Neoplasm Recurrence, Local: genetics / Chromothripsis /
                      Child / Mice / Male / Female / Child, Preschool / Gene
                      Expression Regulation, Neoplastic / Cell Proliferation:
                      genetics / Gene Expression Profiling / Genomic Instability /
                      Clone Cells / Hedgehog Proteins (NLM Chemicals) / SHH
                      protein, human (NLM Chemicals)},
      cin          = {B260 / B420 / W192 / B320 / B062 / W240 / E210 / B300 /
                      HD01},
      ddc          = {500},
      cid          = {I:(DE-He78)B260-20160331 / I:(DE-He78)B420-20160331 /
                      I:(DE-He78)W192-20160331 / I:(DE-He78)B320-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)W240-20160331 /
                      I:(DE-He78)E210-20160331 / I:(DE-He78)B300-20160331 /
                      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:39609432},
      pmc          = {pmc:PMC11604656},
      doi          = {10.1038/s41467-024-54709-w},
      url          = {https://inrepo02.dkfz.de/record/294744},
}