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@ARTICLE{Koelsche:136745,
      author       = {C. Koelsche$^*$ and M. Mynarek and D. Schrimpf$^*$ and L.
                      Bertero and J. Serrano and F. Sahm$^*$ and D. E. Reuss$^*$
                      and Y. Hou and D. Baumhoer and C. Vokuhl and U. Flucke and
                      I. Petersen and W. Brück and S. Rutkowski and S. C.
                      Zambrano and J. L. Garcia Leon and R. Y. Diaz Coronado and
                      M. Gessler and O. M. Tirado and J. Mora and J. Alonso and X.
                      Garcia Del Muro and M. Esteller and D. Sturm$^*$ and J.
                      Ecker$^*$ and T. Milde$^*$ and S. Pfister$^*$ and A.
                      Korshunov$^*$ and M. Snuderl and G. Mechtersheimer and U.
                      Schüller and D. Jones$^*$ and A. von Deimling$^*$},
      title        = {{P}rimary intracranial spindle cell sarcoma with
                      rhabdomyosarcoma-like features share a highly distinct
                      methylation profile and {DICER}1 mutations.},
      journal      = {Acta neuropathologica},
      volume       = {136},
      number       = {2},
      issn         = {1432-0533},
      address      = {Berlin},
      publisher    = {Springer},
      reportid     = {DKFZ-2018-01183},
      pages        = {327 - 337},
      year         = {2018},
      abstract     = {Patients with DICER1 predisposition syndrome have an
                      increased risk to develop pleuropulmonary blastoma, cystic
                      nephroma, embryonal rhabdomyosarcoma, and several other rare
                      tumor entities. In this study, we identified 22 primary
                      intracranial sarcomas, including 18 in pediatric patients,
                      with a distinct methylation signature detected by
                      array-based DNA-methylation profiling. In addition, two
                      uterine rhabdomyosarcomas sharing identical features were
                      identified. Gene panel sequencing of the 22 intracranial
                      sarcomas revealed the almost unifying feature of DICER1
                      hotspot mutations (21/22; $95\%)$ and a high frequency of
                      co-occurring TP53 mutations (12/22; $55\%).$ In addition,
                      17/22 $(77\%)$ sarcomas exhibited alterations in the
                      mitogen-activated protein kinase pathway, most frequently
                      affecting the mutational hotspots of KRAS (8/22; $36\%)$ and
                      mutations or deletions of NF1 (7/22; $32\%),$ followed by
                      mutations of FGFR4 (2/22; $9\%),$ NRAS (2/22; $9\%),$ and
                      amplification of EGFR (1/22; $5\%).$ A germline DICER1
                      mutation was detected in two of five cases with
                      constitutional DNA available. Notably, none of the patients
                      showed evidence of a cancer-related syndrome at the time of
                      diagnosis. In contrast to the genetic findings, the
                      morphological features of these tumors were less
                      distinctive, although rhabdomyoblasts or rhabdomyoblast-like
                      cells could retrospectively be detected in all cases. The
                      identified combination of genetic events indicates a
                      relationship between the intracranial tumors analyzed and
                      DICER1 predisposition syndrome-associated sarcomas such as
                      embryonal rhabdomyosarcoma or the recently described group
                      of anaplastic sarcomas of the kidney. However, the
                      intracranial tumors in our series were initially interpreted
                      to represent various tumor types, but rhabdomyosarcoma was
                      not among the typical differential diagnoses considered.
                      Given the rarity of intracranial sarcomas, this molecularly
                      clearly defined group comprises a considerable fraction
                      thereof. We therefore propose the designation 'spindle cell
                      sarcoma with rhabdomyosarcoma-like features, DICER1 mutant'
                      for this intriguing group.},
      cin          = {G380 / L101 / B062 / G340 / G702},
      ddc          = {610},
      cid          = {I:(DE-He78)G380-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)G340-20160331 /
                      I:(DE-He78)G702-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29881993},
      doi          = {10.1007/s00401-018-1871-6},
      url          = {https://inrepo02.dkfz.de/record/136745},
}