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@ARTICLE{Penkert:168525,
      author       = {J. Penkert and A. Märtens and M. Seifert and B. Auber and
                      K. Derlin and U. Hille-Betz and P. Hörmann and N. Klopp and
                      J. Prokein and L. Schlicker$^*$ and F. Wacker and H.
                      Wallaschek and B. Schlegelberger and K. Hiller and T.
                      Ripperger and T. Illig},
      title        = {{P}lasma {M}etabolome {S}ignature {I}ndicative of {BRCA}1
                      {G}ermline {S}tatus {I}ndependent of {C}ancer {I}ncidence.},
      journal      = {Frontiers in oncology},
      volume       = {11},
      issn         = {2234-943X},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2021-00957},
      pages        = {627217},
      year         = {2021},
      note         = {Division of Tumour Metabolism and Microenvironment, German
                      Cancer Research Center (DKFZ), Heidelberg, Germany.},
      abstract     = {Individuals carrying a pathogenic germline variant in the
                      breast cancer predisposition gene BRCA1 (gBRCA1+) are prone
                      to developing breast cancer. Apart from its well-known role
                      in DNA repair, BRCA1 has been shown to powerfully impact
                      cellular metabolism. While, in general, metabolic
                      reprogramming was named a hallmark of cancer, disrupted
                      metabolism has also been suggested to drive cancer cell
                      evolution and malignant transformation by critically
                      altering microenvironmental tissue integrity. Systemic
                      metabolic effects induced by germline variants in cancer
                      predisposition genes have been demonstrated before. Whether
                      or not systemic metabolic alterations exist in gBRCA1+
                      individuals independent of cancer incidence has not been
                      investigated yet. We therefore profiled the plasma
                      metabolome of 72 gBRCA1+ women and 72 age-matched female
                      controls, none of whom (carriers and non-carriers) had a
                      prior cancer diagnosis and all of whom were cancer-free
                      during the follow-up period. We detected one single
                      metabolite, pyruvate, and two metabolite ratios involving
                      pyruvate, lactate, and a metabolite of yet unknown
                      structure, significantly altered between the two cohorts. A
                      machine learning signature of metabolite ratios was able to
                      correctly distinguish between gBRCA1+ and controls in
                      $~82\%.$ The results of this study point to innate systemic
                      metabolic differences in gBRCA1+ women independent of cancer
                      incidence and raise the question as to whether or not
                      constitutional alterations in energy metabolism may be
                      involved in the etiology of BRCA1-associated breast cancer.},
      keywords     = {BRCA1 germline mutation (Other) / HIF1 alpha (Other) / NAD+
                      balance (Other) / aerobic glycolysis (Other) / breast cancer
                      (Other) / energy metabolism (Other) / lactate (Other) /
                      plasma metabolome (Other)},
      cin          = {A410},
      ddc          = {610},
      cid          = {I:(DE-He78)A410-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33898308},
      pmc          = {pmc:PMC8058469},
      doi          = {10.3389/fonc.2021.627217},
      url          = {https://inrepo02.dkfz.de/record/168525},
}