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@ARTICLE{Bochtler:179572,
      author       = {T. Bochtler$^*$ and T. Wohlfromm$^*$ and T. Hielscher$^*$
                      and D. Stichel$^*$ and M. Pouyiourou$^*$ and B. Kraft$^*$
                      and O. Neumann and V. Endris and A. von Deimling$^*$ and A.
                      Stenzinger and A. Krämer$^*$},
      title        = {{P}rognostic {I}mpact of {C}opy {N}umber {A}lterations and
                      {T}umor {M}utational {B}urden in {C}arcinoma of {U}nknown
                      {P}rimary.},
      journal      = {Genes, chromosomes $\&$ cancer},
      volume       = {61},
      number       = {9},
      issn         = {1045-2257},
      address      = {New York, NY},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2022-00750},
      pages        = {551-560},
      year         = {2022},
      note         = {#EA:A360#LA:A360# / 2022 Sep;61(9):551-560},
      abstract     = {Chromosomal aberrations are known to drive metastatic
                      spread, but their profile is still elusive in carcinoma of
                      unknown primary (CUP). Therefore, it was the aim of this
                      study to characterize the chromosomal aberration pattern in
                      CUP depending on histological and clinical features and to
                      assess its prognostic impact together with chromothripsis,
                      tumor mutational burden (TMB), microsatellite instability
                      (MSI) and mutational profiles as potential prognostic
                      biomarkers.Chromosomal aberrations and chromothripsis were
                      detected by methylation-based copy number variation (CNV)
                      analysis, whereas TMB and MSI were calculated based on large
                      next generation sequencing (NGS) panels. Putative primaries
                      were assigned by consensus between two independent
                      oncologists.CNV losses varied depending on putative
                      primaries and were more abundant in patients harboring TP53
                      mutations and/or deletions 17p. CNV loss was prognostically
                      adverse in localized CUP treated with surgery and/or
                      radiotherapy, but not in disseminated poor risk CUP treated
                      with palliative chemotherapy. CNV loss also worsened the
                      prognosis in squamous cell CUP. Chromothripsis was detected
                      in 18/59 $(30.5\%)$ patients without prognostic effect. TMB
                      was highest in cases with microsatellite instability,
                      squamous cell histology and with lung, anal or cervical
                      putative primaries.Overall, CNV, chromothripsis, TMB and MSI
                      profiles in CUP are reminescent of biological
                      characteristics known from other cancer entities without a
                      unifying CUP-specific signature. Markedly, high-level CNV
                      loss is an adverse predictive biomarker in localized but not
                      disseminated chemotherapy treated CUP. This implies that
                      chromosomal losses drive CUP progression, but also increase
                      susceptibility to chemotherapy, with both effects apparently
                      leveling out in disseminated CUP.},
      keywords     = {Carcinoma of unknown primary (CUP) (Other) / chromosomal
                      instability (Other) / chromothripsis (Other) / copy number
                      variations (CNV) (Other) / mutational profile (Other) /
                      prognosis (Other) / tumor mutational burden (TMB) (Other)},
      cin          = {A360 / C060 / B300},
      ddc          = {610},
      cid          = {I:(DE-He78)A360-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)B300-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35430765},
      doi          = {10.1002/gcc.23047},
      url          = {https://inrepo02.dkfz.de/record/179572},
}