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@ARTICLE{Jahn:181321,
      author       = {A. Jahn$^*$ and A. Rump$^*$ and T. Widmann$^*$ and C.
                      Heining$^*$ and P. Horak$^*$ and B. Hutter$^*$ and N.
                      Paramasivam$^*$ and S. Uhrig$^*$ and L. Gieldon and S.
                      Drukewitz$^*$ and A. Kübler and M. Bermudez and K. Hackmann
                      and J. Porrmann and J. Wagner and M. Arlt and M. Franke and
                      J. Fischer and Z. Kowalzyk and D. William$^*$ and V. Weth
                      and S. Oster$^*$ and M. A. Fröhlich$^*$ and J. Hüllein$^*$
                      and C. Valle González$^*$ and S. Kreutzfeldt$^*$ and A.
                      Mock$^*$ and C. Heilig$^*$ and D. Lipka$^*$ and L.
                      Möhrmann$^*$ and D. Hanf$^*$ and M.-V. Teleanu$^*$ and M.
                      Allgäuer and L. Ruhnke and O. Kutz and A. Knurr$^*$ and A.
                      Laßmann$^*$ and V. Endris and O. Neumann and R. Penzel and
                      K. Beck$^*$ and D. Richter$^*$ and U. Winter$^*$ and S.
                      Wolf$^*$ and K. Pfütze$^*$ and C. Geörg$^*$ and B.
                      Meissburger$^*$ and I. Buchhalter$^*$ and M. Augustin and W.
                      E. Aulitzky and P. Hohenberger and M. Kroiss and P.
                      Schirmacher$^*$ and R. Schlenk$^*$ and U. Keilholz$^*$ and
                      F. Klauschen$^*$ and G. Folprecht$^*$ and S. Bauer$^*$ and
                      J. Siveke$^*$ and C. H. Brandts$^*$ and T. Kindler$^*$ and
                      M. Börries$^*$ and A. L. Illert$^*$ and N. von Bubnoff and
                      P. J. Jost$^*$ and K. H. Metzeler and M. Bitzer$^*$ and K.
                      Schulze Osthoff$^*$ and C. von Kalle and B. Brors$^*$ and A.
                      Stenzinger$^*$ and W. Weichert$^*$ and D. Hübschmann$^*$
                      and S. Fröhling$^*$ and H. Glimm$^*$ and E. Schröck$^*$
                      and B. Klink$^*$},
      title        = {{C}omprehensive cancer predisposition testing within the
                      prospective {MASTER} trial identifies hereditary cancer
                      patients and supports treatment decisions for rare cancers.},
      journal      = {Annals of oncology},
      volume       = {33},
      number       = {11},
      issn         = {0923-7534},
      address      = {Amsterdam [u.a.},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2022-01948},
      pages        = {1186-1199},
      year         = {2022},
      note         = {2022 Nov;33(11):1186-1199},
      abstract     = {Germline variant evaluation in precision oncology opens new
                      paths towards the identification of patients with genetic
                      tumor risk syndromes and the exploration of therapeutic
                      relevance. Here, we present the results of germline variant
                      analysis and their clinical implications in a precision
                      oncology study for patients with predominantly rare
                      cancers.Matched tumor and control genome/exome and RNA
                      sequencing was performed for 1,485 patients with rare
                      cancers $(79\%)$ and/or young adults $(77\%$ younger than 51
                      years) in the NCT/DKTK MASTER trial, a German multicenter,
                      prospective observational precision oncology study. Clinical
                      and therapeutic relevance of prospective pathogenic germline
                      variant (PGV) evaluation was analyzed and compared to other
                      precision oncology studies.Ten percent of patients (n=157)
                      harbored PGVs in 35 genes associated with autosomal dominant
                      cancer predisposition, whereof up to $75\%$ were unknown
                      before study participation. Another five percent of patients
                      (n=75) were heterozygous carriers for recessive genetic
                      tumor risk syndromes. Particularly high PGV yields were
                      found in patients with gastrointestinal stromal tumors
                      (GISTs) $(28\%,$ 11/40), and more specific in wild-type
                      GISTS $(50\%,$ n=10/20), leiomyosarcomas $(21\%,$ n=19/89),
                      and hepatopancreaticobiliary cancers $(16\%,$ n=16/97).
                      Forty-five percent of PGVs (n=100/221) supported treatment
                      recommendations, and its implementation led to a clinical
                      benefit in $40\%$ of patients (n=10/25). A comparison of
                      different precision oncology studies revealed variable PGV
                      yields and considerable differences in germline variant
                      analysis workflows. We therefore propose a detailed workflow
                      for germline variant evaluation.Genetic germline testing in
                      patients with rare cancers can identify the very first
                      patient in a hereditary cancer family and can lead to
                      clinical benefit in a broad range of entities. Its routine
                      implementation in precision oncology accompanied by the
                      harmonization of germline variant evaluation workflows will
                      increase clinical benefit and boost research.},
      keywords     = {biomarker (Other) / hereditary cancer (Other) / precision
                      medicine (Other) / prevention (Other) / rare cancer (Other)
                      / targeted therapy (Other)},
      cin          = {DD01 / HD01 / B340 / B330 / M130 / W190 / W610 / BE01 /
                      ED01 / FM01 / FR01 / MU01 / TU01 / W010},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B340-20160331 / I:(DE-He78)B330-20160331 /
                      I:(DE-He78)M130-20160331 / I:(DE-He78)W190-20160331 /
                      I:(DE-He78)W610-20160331 / I:(DE-He78)BE01-20160331 /
                      I:(DE-He78)ED01-20160331 / I:(DE-He78)FM01-20160331 /
                      I:(DE-He78)FR01-20160331 / I:(DE-He78)MU01-20160331 /
                      I:(DE-He78)TU01-20160331 / I:(DE-He78)W010-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35988656},
      doi          = {10.1016/j.annonc.2022.07.008},
      url          = {https://inrepo02.dkfz.de/record/181321},
}