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@ARTICLE{Manoochehri:182334,
      author       = {M. Manoochehri$^*$ and N. Borhani$^*$ and C. Gerhäuser$^*$
                      and Y. Assenov$^*$ and M. Schönung$^*$ and T. Hielscher$^*$
                      and B. C. Christensen and M. K. Lee and H.-J. Gröne and D.
                      Lipka$^*$ and T. Brüning and H. Brauch$^*$ and Y.-D. Ko and
                      U. Hamann$^*$},
      title        = {{DNA} methylation biomarkers for non-invasive detection of
                      triple negative breast cancer using liquid biopsy.},
      journal      = {International journal of cancer},
      volume       = {152},
      number       = {5},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2022-02577},
      pages        = {1025-1035},
      year         = {2023},
      note         = {#EA:B070#EA:B072#LA:B070#LA:B072# / 2023 Mar
                      1;152(5):1025-1035},
      abstract     = {Non-invasive detection of aberrant DNA methylation could
                      provide invaluable biomarkers for earlier detection of
                      triple negative breast cancer (TNBC) which could help
                      clinicians with easier and more efficient treatment options.
                      We evaluated genome-wide DNA methylation data derived from
                      TNBC and normal breast tissues, peripheral blood of TNBC
                      cases and controls, and reference samples of sorted blood
                      and mammary cells. Differentially methylated regions (DMRs)
                      between TNBC and normal breast tissues were stringently
                      selected, verified, and externally validated. A
                      machine-learning algorithm was applied to select the top
                      DMRs, which then were evaluated on plasma-derived
                      circulating cell-free DNA (cfDNA) samples of TNBC patients
                      and healthy controls. We identified 23 DMRs accounting for
                      the methylation profile of blood cells and reference mammary
                      cells and then selected six top DMRs for cfDNA analysis. We
                      quantified un-/methylated copies of these DMRs by droplet
                      digital PCR analysis in a plasma test set from TNBC patients
                      and healthy controls and confirmed our findings obtained on
                      tissues. Differential cfDNA methylation was confirmed in an
                      independent validation set of plasma samples. A methylation
                      score combining signatures of the top three DMRs overlapping
                      with the SPAG6, LINC10606, and TBCD/ZNF750 genes had the
                      best capability to discriminate TNBC patients from controls
                      (AUC=0.78 in the test set and AUC=0.74 in validation set).
                      Our findings demonstrate the usefulness of cfDNA-based
                      methylation signatures as non-invasive liquid biopsy markers
                      for the diagnosis of TNBC. This article is protected by
                      copyright. All rights reserved.},
      subtyp        = {Review Article},
      keywords     = {Biomarker (Other) / DNA methylation (Other) / Liquid biopsy
                      (Other) / Non-invasive detection (Other) / Triple Negative
                      Breast Cancer (Other)},
      cin          = {B370 / B072 / B340 / C060 / TU01},
      ddc          = {610},
      cid          = {I:(DE-He78)B370-20160331 / I:(DE-He78)B072-20160331 /
                      I:(DE-He78)B340-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)TU01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36305646},
      doi          = {10.1002/ijc.34337},
      url          = {https://inrepo02.dkfz.de/record/182334},
}