% 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{Koelsche:170013,
      author       = {C. Koelsche and J. K. Benhamida and F. K. F. Kommoss and D.
                      Stichel$^*$ and D. Jones$^*$ and S. M. Pfister$^*$ and C. E.
                      Heilig$^*$ and S. Fröhling$^*$ and A. Stenzinger and R.
                      Buslei and T. Mentzel and D. Baumhoer and M. Ladanyi and C.
                      R. Antonescu and U. Flucke and J. v. Gorp and B.
                      Bode-Lesniewska and A. von Deimling$^*$ and G.
                      Mechtersheimer},
      title        = {{I}ntimal sarcomas and undifferentiated cardiac sarcomas
                      carry mutually exclusive {MDM}2, {MDM}4, and {CDK}6
                      amplifications and share a common {DNA} methylation
                      signature.},
      journal      = {Modern pathology},
      volume       = {34},
      number       = {12},
      issn         = {1530-0285},
      address      = {London},
      publisher    = {Nature Publishing Group},
      reportid     = {DKFZ-2021-01707},
      pages        = {2122-2129},
      year         = {2021},
      note         = {#LA:B300# / 2021 Dec;34(12):2122-2129},
      abstract     = {Undifferentiated mesenchymal tumors arising from the inner
                      lining (intima) of large arteries are classified as intimal
                      sarcomas (ISA) with MDM2 amplification as their molecular
                      hallmark. Interestingly, undifferentiated pleomorphic
                      sarcomas (UPS) of the heart have recently been suggested to
                      represent the cardiac analog of ISA due to morphological
                      overlap and high prevalence of MDM2 amplifications in both
                      neoplasms. However, little is known about ISAs and cardiac
                      UPS without MDM2 amplifications and molecular data
                      supporting their common classification is sparse. Here, we
                      report a series of 35 cases comprising 25 ISAs of the
                      pulmonary artery, one ISA of the renal artery and 9 UPS of
                      the left atrium. Tumors were analyzed utilizing the Illumina
                      Infinium MethylationEPIC BeadChip array, enabling copy
                      number profile generation and unsupervised DNA methylation
                      analysis. DNA methylation patterns were investigated using
                      t-distributed stochastic neighbor embedding (t-SNE)
                      analysis. Histologically, all ISAs and UPS of the left
                      atrium resembled extra-cardiac UPS. All cases exhibited
                      highly complex karyotypes with overlapping patterns between
                      ISA and UPS. 29/35 cases showed mutually exclusive
                      amplifications in the cell-cycle associated oncogenes MDM2
                      (25/35), MDM4 (2/35), and CDK6 (2/35). We further observed
                      recurrent co-amplifications in PDGFRA (21/35), CDK4 (15/35),
                      TERT (11/35), HDAC9 (9/35), and CCND1 (4/35). Sporadic
                      co-amplifications occurred in MYC, MYCN, and MET (each
                      1/35). The tumor suppressor CDKN2A/B was frequently deleted
                      (10/35). Interestingly, DNA methylation profiling (t-SNE)
                      revealed an overlap of ISA and cardiac UPS. This 'ISA'
                      methylation signature was distinct from potential histologic
                      and molecular mimics. In conclusion, our data reveal MDM4
                      and CDK6 amplifications in ISAs and UPS of the left atrium,
                      lacking MDM2 amplification. We further report novel
                      co-amplifications of various oncogenes, which may have
                      therapeutic implications. Finally, the genetic and
                      epigenetic concordance of ISAs and UPS of the left atrium
                      further supports a shared pathogenesis and common
                      classification.},
      cin          = {B300 / HD01 / B360 / B062 / B340},
      ddc          = {610},
      cid          = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B360-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)B340-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34312479},
      doi          = {10.1038/s41379-021-00874-y},
      url          = {https://inrepo02.dkfz.de/record/170013},
}