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@ARTICLE{Johann:277733,
      author       = {P. Johann$^*$ and L. Altendorf and E.-M. Efremova and T.
                      Holsten and M. Steinbügl and K. Nemes and A. Eckhardt and
                      C. Kresbach and M. Bockmayr and A. Koch and C. Haberler and
                      M. Antonelli and J. DeSisto and M. U. Schuhmann and P.
                      Hauser and R. Siebert and S. Bens and M. Kool$^*$ and A. L.
                      Green and M. Hasselblatt and M. C. Frühwald and U.
                      Schüller},
      title        = {{R}ecurrent atypical teratoid/rhabdoid tumors ({AT}/{RT})
                      reveal discrete features of progression on histology,
                      epigenetics, copy number profiling, and transcriptomics.},
      journal      = {Acta neuropathologica},
      volume       = {146},
      number       = {3},
      issn         = {0001-6322},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2023-01450},
      pages        = {527-541},
      year         = {2023},
      note         = {#EA:B062# / 2023 Sep;146(3):527-541},
      abstract     = {Atypical teratoid/rhabdoid tumors (AT/RT) are the most
                      common malignant brain tumors manifesting in infancy. They
                      split into four molecular types. The major three (AT/RT-SHH,
                      AT/RT-TYR, and AT/RT-MYC) all carry mutations in SMARCB1,
                      the fourth quantitatively smaller type is characterized by
                      SMARCA4 mutations (AT/RT-SMARCA4). Molecular characteristics
                      of disease recurrence or metastatic spread, which go along
                      with a particularly dismal outcome, are currently unclear.
                      Here, we investigated tumor tissue from 26 patients affected
                      by AT/RT to identify signatures of recurrences in comparison
                      with matched primary tumor samples. Microscopically, AT/RT
                      recurrences demonstrated a loss of architecture and
                      significantly enhanced mitotic activity as compared to their
                      related primary tumors. Based on DNA methylation profiling,
                      primary tumor and related recurrence were grossly similar,
                      but three out of 26 tumors belonged to a different molecular
                      type or subtype after second surgery compared to related
                      primary lesions. Copy number variations (CNVs) differed in
                      six cases, showing novel gains on chromosome 1q or losses of
                      chromosome 10 in recurrences as the most frequent
                      alterations. To consolidate these observations, our cohort
                      was combined with a data set of unmatched primary and
                      recurrent AT/RT, which demonstrated chromosome 1q gain and
                      10 loss in $18\%$ (n = 7) and $11\%$ (n = 4) of the
                      recurrences (n = 38) as compared to $7\%$ (n = 3) and $0\%$
                      (n = 0) in the primary tumors (n = 44), respectively.
                      Similar to the observations made by DNA methylation
                      profiling, RNA sequencing of our cohort revealed AT/RT
                      primary tumors and matched recurrences clustering closely
                      together. However, a number of genes showed significantly
                      altered expression in AT/RT-SHH recurrences. Many of them
                      are known tumor driving growth factors, involved in
                      embryonal development and tumorigenesis, or are
                      cell-cycle-associated. Overall, our work identifies subtle
                      molecular changes that occur in the course of the disease
                      and that may help define novel therapeutic targets for AT/RT
                      recurrences.},
      keywords     = {AT/RT (Other) / DNA methylation (Other) / Pediatric cancer
                      (Other) / RNA sequencing (Other) / Recurrent tumor (Other) /
                      Rhabdoid tumor (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:37450044},
      doi          = {10.1007/s00401-023-02608-7},
      url          = {https://inrepo02.dkfz.de/record/277733},
}