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@ARTICLE{Tang:130650,
      author       = {Q. Tang$^*$ and T. Holland-Letz$^*$ and A. Slynko$^*$ and
                      K. Cuk$^*$ and F. Marme and S. Schott and J. Heil and B. Qu
                      and M. Golatta and M. Bewerunge-Hudler and C. Sutter and H.
                      Surowy$^*$ and B. Wappenschmidt and R. Schmutzler and M.
                      Hoth and P. Bugert and C. R. Bartram and C. Sohn and A.
                      Schneeweiss and R. Yang$^*$ and B. Burwinkel$^*$},
      title        = {{DNA} methylation array analysis identifies breast cancer
                      associated {RPTOR}, {MGRN}1 and {RAPSN} hypomethylation in
                      peripheral blood {DNA}.},
      journal      = {OncoTarget},
      volume       = {7},
      number       = {39},
      issn         = {1949-2553},
      address      = {[S.l.]},
      publisher    = {Impact Journals LLC},
      reportid     = {DKFZ-2017-05728},
      pages        = {64191 - 64202},
      year         = {2016},
      abstract     = {DNA methylation changes in peripheral blood DNA have been
                      shown to be associated with solid tumors. We sought to
                      identify methylation alterations in whole blood DNA that are
                      associated with breast cancer (BC). Epigenome-wide DNA
                      methylation profiling on blood DNA from BC cases and healthy
                      controls was performed by applying Infinium
                      HumanMethylation450K BeadChips. Promising CpG sites were
                      selected and validated in three independent larger sample
                      cohorts via MassARRAY EpiTyper assays. CpG sites located in
                      three genes (cg06418238 in RPTOR, cg00736299 in MGRN1 and
                      cg27466532 in RAPSN), which showed significant
                      hypomethylation in BC patients compared to healthy controls
                      in the discovery cohort (p < 1.00 x 10-6) were selected and
                      successfully validated in three independent cohorts
                      (validation I, n =211; validation II, n=378; validation III,
                      n=520). The observed methylation differences are likely not
                      cell-type specific, as the differences were only seen in
                      whole blood, but not in specific sub cell-types of
                      leucocytes. Moreover, we observed in quartile analysis that
                      women in the lower methylation quartiles of these three loci
                      had higher ORs than women in the higher quartiles. The
                      combined AUC of three loci was 0.79 $(95\%CI$ 0.73-0.85) in
                      validation cohort I, and was 0.60 $(95\%CI$ 0.54-0.66) and
                      0.62 $(95\%CI$ 0.57-0.67) in validation cohort II and III,
                      respectively. Our study suggests that hypomethylation of CpG
                      sites in RPTOR, MGRN1 and RAPSN in blood is associated with
                      BC and might serve as blood-based marker supplements for BC
                      if these could be verified in prospective studies.},
      cin          = {C060 / C080},
      ddc          = {610},
      cid          = {I:(DE-He78)C060-20160331 / I:(DE-He78)C080-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:27577081},
      pmc          = {pmc:PMC5325435},
      doi          = {10.18632/oncotarget.11640},
      url          = {https://inrepo02.dkfz.de/record/130650},
}