% 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{Okonechnikov:300822,
      author       = {K. Okonechnikov$^*$ and P. K. Joshi$^*$ and V. Körber$^*$
                      and A. Rademacher$^*$ and M. Bortolomeazzi$^*$ and J.-P.
                      Mallm$^*$ and J. Vaillant$^*$ and P. B. G. da Silva$^*$ and
                      B. Statz$^*$ and M. Sepp and I. Sarropoulos and T. Yamada
                      and A. Wittmann$^*$ and K. Schramm$^*$ and M.
                      Blattner-Johnson$^*$ and P. Fiesel$^*$ and B. Jones$^*$ and
                      N. Jäger$^*$ and T. Milde$^*$ and K. Pajtler$^*$ and C. M.
                      van Tilburg$^*$ and O. Witt$^*$ and K. Bochennek and K. J.
                      Weber$^*$ and L. Nonnenmacher and C. Reimann and D. R.
                      Ghasemi$^*$ and U. Schüller and M. Mynarek and S. Rutkowski
                      and D. Jones$^*$ and A. Korshunov$^*$ and K. Rippe$^*$ and
                      F. Westermann$^*$ and S. Thongjuea$^*$ and T. Höfer$^*$ and
                      H. Kaessmann$^*$ and L. Kutscher$^*$ and S. Pfister$^*$},
      title        = {{O}ncogene aberrations drive medulloblastoma progression,
                      not initiation.},
      journal      = {Nature},
      volume       = {642},
      number       = {8069},
      issn         = {0028-0836},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2025-00936},
      pages        = {1062-1072},
      year         = {2025},
      note         = {DKFZ-ZMBH Alliance /
                      #EA:B062#EA:B430#EA:B086#LA:B430#LA:B062# / 2025
                      Jun;642(8069):1062-1072},
      abstract     = {Despite recent advances in understanding disease biology,
                      treatment of group 3/4 medulloblastoma remains a therapeutic
                      challenge in paediatric neuro-oncology1. Bulk-omics
                      approaches have identified considerable intertumoural
                      heterogeneity in group 3/4 medulloblastoma, including the
                      presence of clear single-gene oncogenic drivers in only a
                      subset of cases, whereas in most cases, large-scale copy
                      number aberrations prevail2,3. However, intratumoural
                      heterogeneity, the role of oncogene aberrations, and broad
                      copy number variation in tumour evolution and treatment
                      resistance remain poorly understood. To dissect this
                      interplay, we used single-cell technologies (single-nucleus
                      RNA sequencing (snRNA-seq), single-nucleus assay for
                      transposase-accessible chromatin with high-throughput
                      sequencing (snATAC-seq) and spatial transcriptomics) on a
                      cohort of group 3/4 medulloblastoma with known alterations
                      in the oncogenes MYC, MYCN and PRDM6. We show that
                      large-scale chromosomal aberrations are early
                      tumour-initiating events, whereas the single-gene oncogenic
                      events arise late and are typically subclonal, but MYC can
                      become clonal upon disease progression to drive further
                      tumour development and therapy resistance. Spatial
                      transcriptomics shows that the subclones are mostly
                      interspersed across tumour tissue, but clear segregation is
                      also present. Using a population genetics model, we estimate
                      medulloblastoma initiation in the cerebellar unipolar brush
                      cell lineage starting from the first gestational trimester.
                      Our findings demonstrate how single-cell technologies can be
                      applied for early detection and diagnosis of this fatal
                      disease.},
      cin          = {B062 / HD01 / B430 / B086 / B066 / W192 / B360 / B300 /
                      B310 / FM01 / B087},
      ddc          = {500},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B430-20160331 / I:(DE-He78)B086-20160331 /
                      I:(DE-He78)B066-20160331 / I:(DE-He78)W192-20160331 /
                      I:(DE-He78)B360-20160331 / I:(DE-He78)B300-20160331 /
                      I:(DE-He78)B310-20160331 / I:(DE-He78)FM01-20160331 /
                      I:(DE-He78)B087-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40335697},
      doi          = {10.1038/s41586-025-08973-5},
      url          = {https://inrepo02.dkfz.de/record/300822},
}