Evaluation of Different Biomarkers to Predict Individual Radiosensitivity in an Inter-Laboratory Comparison–Lessons for Future Studies
Identifieur interne : 002A19 ( Pmc/Checkpoint ); précédent : 002A18; suivant : 002A20Evaluation of Different Biomarkers to Predict Individual Radiosensitivity in an Inter-Laboratory Comparison–Lessons for Future Studies
Auteurs : Burkhard Greve [Allemagne] ; Tobias Bölling [Allemagne] ; Susanne Amler [Allemagne] ; Ute Rössler [Allemagne] ; Maria Gomolka [Allemagne] ; Claudia Mayer [Allemagne] ; Odilia Popanda [Allemagne] ; Kristin Dreffke [Allemagne] ; Astrid Rickinger [Allemagne] ; Eberhard Fritz [Allemagne] ; Friederike Eckardt-Schupp [Allemagne] ; Christina Sauerland [Allemagne] ; Herbert Braselmann [Allemagne] ; Wiebke Sauter [Allemagne] ; Thomas Illig [Allemagne] ; Dorothea Riesenbeck [Allemagne] ; Stefan Könemann [Allemagne] ; Normann Willich [Allemagne] ; Simone Mörtl [Allemagne] ; Hans Theodor Eich [Allemagne] ; Peter Schmezer [Allemagne]Source :
- PLoS ONE [ 1932-6203 ] ; 2012.
Abstract
Radiotherapy is a powerful cure for several types of solid tumours, but its application is often limited because of severe side effects in individual patients. With the aim to find biomarkers capable of predicting normal tissue side reactions we analysed the radiation responses of cells from individual head and neck tumour and breast cancer patients of different clinical radiosensitivity in a multicentric study. Multiple parameters of cellular radiosensitivity were analysed in coded samples of peripheral blood lymphocytes (PBLs) and derived lymphoblastoid cell lines (LCLs) from 15 clinical radio-hypersensitive tumour patients and compared to age- and sex-matched non-radiosensitive patient controls and 15 lymphoblastoid cell lines from age- and sex- matched healthy controls of the KORA study. Experimental parameters included ionizing radiation (IR)-induced cell death (AnnexinV), induction and repair of DNA strand breaks (Comet assay), induction of yH2AX foci (as a result of DNA double strand breaks), and whole genome expression analyses. Considerable inter-individual differences in IR-induced DNA strand breaks and their repair and/or cell death could be detected in primary and immortalised cells with the applied assays. The group of clinically radiosensitive patients was not unequivocally distinguishable from normal responding patients nor were individual overreacting patients in the test system unambiguously identified by two different laboratories. Thus, the
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DOI: 10.1371/journal.pone.0047185
PubMed: 23110060
PubMed Central: 3479094
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Radiotherapy, University Hospital of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Radiotherapy, University Hospital of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Amler, Susanne" sort="Amler, Susanne" uniqKey="Amler S" first="Susanne" last="Amler">Susanne Amler</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Biostatistics and Clinical Research, University of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Rossler, Ute" sort="Rossler, Ute" uniqKey="Rossler U" first="Ute" last="Rössler">Ute Rössler</name><affiliation wicri:level="1"><nlm:aff id="aff8"><addr-line>Federal Office for Radiation Protection, Department of Radiation Protection and Health, Oberschleissheim, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Federal Office for Radiation Protection, Department of Radiation Protection and Health, Oberschleissheim</wicri:regionArea><wicri:noRegion>Oberschleissheim</wicri:noRegion><wicri:noRegion>Oberschleissheim</wicri:noRegion><wicri:noRegion>Oberschleissheim</wicri:noRegion></affiliation></author><author><name sortKey="Gomolka, Maria" sort="Gomolka, Maria" uniqKey="Gomolka M" first="Maria" last="Gomolka">Maria Gomolka</name><affiliation wicri:level="1"><nlm:aff id="aff8"><addr-line>Federal Office for Radiation Protection, Department of Radiation Protection and Health, Oberschleissheim, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Federal Office for Radiation Protection, Department of Radiation Protection and Health, Oberschleissheim</wicri:regionArea><wicri:noRegion>Oberschleissheim</wicri:noRegion><wicri:noRegion>Oberschleissheim</wicri:noRegion><wicri:noRegion>Oberschleissheim</wicri:noRegion></affiliation></author><author><name sortKey="Mayer, Claudia" sort="Mayer, Claudia" uniqKey="Mayer C" first="Claudia" last="Mayer">Claudia Mayer</name><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Division of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), Heidelberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Popanda, Odilia" sort="Popanda, Odilia" uniqKey="Popanda O" first="Odilia" last="Popanda">Odilia Popanda</name><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Division of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), Heidelberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Dreffke, Kristin" sort="Dreffke, Kristin" uniqKey="Dreffke K" first="Kristin" last="Dreffke">Kristin Dreffke</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI), Jena, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI), Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Rickinger, Astrid" sort="Rickinger, Astrid" uniqKey="Rickinger A" first="Astrid" last="Rickinger">Astrid Rickinger</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Institute of Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Fritz, Eberhard" sort="Fritz, Eberhard" uniqKey="Fritz E" first="Eberhard" last="Fritz">Eberhard Fritz</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI), Jena, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI), Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Eckardt Schupp, Friederike" sort="Eckardt Schupp, Friederike" uniqKey="Eckardt Schupp F" first="Friederike" last="Eckardt-Schupp">Friederike Eckardt-Schupp</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Institute of Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Sauerland, Christina" sort="Sauerland, Christina" uniqKey="Sauerland C" first="Christina" last="Sauerland">Christina Sauerland</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Biostatistics and Clinical Research, University of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Braselmann, Herbert" sort="Braselmann, Herbert" uniqKey="Braselmann H" first="Herbert" last="Braselmann">Herbert Braselmann</name><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Institute of Molecular Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Molecular Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Sauter, Wiebke" sort="Sauter, Wiebke" uniqKey="Sauter W" first="Wiebke" last="Sauter">Wiebke Sauter</name><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Institute of Epidemiology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Epidemiology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Illig, Thomas" sort="Illig, Thomas" uniqKey="Illig T" first="Thomas" last="Illig">Thomas Illig</name><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Institute of Epidemiology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Epidemiology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Riesenbeck, Dorothea" sort="Riesenbeck, Dorothea" uniqKey="Riesenbeck D" first="Dorothea" last="Riesenbeck">Dorothea Riesenbeck</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Radiotherapy, University Hospital of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Konemann, Stefan" sort="Konemann, Stefan" uniqKey="Konemann S" first="Stefan" last="Könemann">Stefan Könemann</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Radiotherapy, University Hospital of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Willich, Normann" sort="Willich, Normann" uniqKey="Willich N" first="Normann" last="Willich">Normann Willich</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Radiotherapy, University Hospital of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Mortl, Simone" sort="Mortl, Simone" uniqKey="Mortl S" first="Simone" last="Mörtl">Simone Mörtl</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Institute of Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Eich, Hans Theodor" sort="Eich, Hans Theodor" uniqKey="Eich H" first="Hans Theodor" last="Eich">Hans Theodor Eich</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Radiotherapy, University Hospital of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Schmezer, Peter" sort="Schmezer, Peter" uniqKey="Schmezer P" first="Peter" last="Schmezer">Peter Schmezer</name><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Division of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), Heidelberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23110060</idno><idno type="pmc">3479094</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479094</idno><idno type="RBID">PMC:3479094</idno><idno type="doi">10.1371/journal.pone.0047185</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">004450</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">004450</idno><idno type="wicri:Area/Pmc/Curation">004449</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">004449</idno><idno type="wicri:Area/Pmc/Checkpoint">002A19</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">002A19</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Evaluation of Different Biomarkers to Predict Individual Radiosensitivity in an Inter-Laboratory Comparison–Lessons for Future Studies</title><author><name sortKey="Greve, Burkhard" sort="Greve, Burkhard" uniqKey="Greve B" first="Burkhard" last="Greve">Burkhard Greve</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Radiotherapy, University Hospital of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Bolling, Tobias" sort="Bolling, Tobias" uniqKey="Bolling T" first="Tobias" last="Bölling">Tobias Bölling</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Radiotherapy, University Hospital of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Amler, Susanne" sort="Amler, Susanne" uniqKey="Amler S" first="Susanne" last="Amler">Susanne Amler</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Biostatistics and Clinical Research, University of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Rossler, Ute" sort="Rossler, Ute" uniqKey="Rossler U" first="Ute" last="Rössler">Ute Rössler</name><affiliation wicri:level="1"><nlm:aff id="aff8"><addr-line>Federal Office for Radiation Protection, Department of Radiation Protection and Health, Oberschleissheim, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Federal Office for Radiation Protection, Department of Radiation Protection and Health, Oberschleissheim</wicri:regionArea><wicri:noRegion>Oberschleissheim</wicri:noRegion><wicri:noRegion>Oberschleissheim</wicri:noRegion><wicri:noRegion>Oberschleissheim</wicri:noRegion></affiliation></author><author><name sortKey="Gomolka, Maria" sort="Gomolka, Maria" uniqKey="Gomolka M" first="Maria" last="Gomolka">Maria Gomolka</name><affiliation wicri:level="1"><nlm:aff id="aff8"><addr-line>Federal Office for Radiation Protection, Department of Radiation Protection and Health, Oberschleissheim, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Federal Office for Radiation Protection, Department of Radiation Protection and Health, Oberschleissheim</wicri:regionArea><wicri:noRegion>Oberschleissheim</wicri:noRegion><wicri:noRegion>Oberschleissheim</wicri:noRegion><wicri:noRegion>Oberschleissheim</wicri:noRegion></affiliation></author><author><name sortKey="Mayer, Claudia" sort="Mayer, Claudia" uniqKey="Mayer C" first="Claudia" last="Mayer">Claudia Mayer</name><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Division of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), Heidelberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Popanda, Odilia" sort="Popanda, Odilia" uniqKey="Popanda O" first="Odilia" last="Popanda">Odilia Popanda</name><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Division of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), Heidelberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Dreffke, Kristin" sort="Dreffke, Kristin" uniqKey="Dreffke K" first="Kristin" last="Dreffke">Kristin Dreffke</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI), Jena, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI), Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Rickinger, Astrid" sort="Rickinger, Astrid" uniqKey="Rickinger A" first="Astrid" last="Rickinger">Astrid Rickinger</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Institute of Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Fritz, Eberhard" sort="Fritz, Eberhard" uniqKey="Fritz E" first="Eberhard" last="Fritz">Eberhard Fritz</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI), Jena, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI), Jena</wicri:regionArea><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion><wicri:noRegion>Jena</wicri:noRegion></affiliation></author><author><name sortKey="Eckardt Schupp, Friederike" sort="Eckardt Schupp, Friederike" uniqKey="Eckardt Schupp F" first="Friederike" last="Eckardt-Schupp">Friederike Eckardt-Schupp</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Institute of Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Sauerland, Christina" sort="Sauerland, Christina" uniqKey="Sauerland C" first="Christina" last="Sauerland">Christina Sauerland</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Biostatistics and Clinical Research, University of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Braselmann, Herbert" sort="Braselmann, Herbert" uniqKey="Braselmann H" first="Herbert" last="Braselmann">Herbert Braselmann</name><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Institute of Molecular Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Molecular Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Sauter, Wiebke" sort="Sauter, Wiebke" uniqKey="Sauter W" first="Wiebke" last="Sauter">Wiebke Sauter</name><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Institute of Epidemiology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Epidemiology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Illig, Thomas" sort="Illig, Thomas" uniqKey="Illig T" first="Thomas" last="Illig">Thomas Illig</name><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Institute of Epidemiology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Epidemiology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Riesenbeck, Dorothea" sort="Riesenbeck, Dorothea" uniqKey="Riesenbeck D" first="Dorothea" last="Riesenbeck">Dorothea Riesenbeck</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Radiotherapy, University Hospital of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Konemann, Stefan" sort="Konemann, Stefan" uniqKey="Konemann S" first="Stefan" last="Könemann">Stefan Könemann</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Radiotherapy, University Hospital of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Willich, Normann" sort="Willich, Normann" uniqKey="Willich N" first="Normann" last="Willich">Normann Willich</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Radiotherapy, University Hospital of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Mortl, Simone" sort="Mortl, Simone" uniqKey="Mortl S" first="Simone" last="Mörtl">Simone Mörtl</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Institute of Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg</wicri:regionArea><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion><wicri:noRegion>Neuherberg</wicri:noRegion></affiliation></author><author><name sortKey="Eich, Hans Theodor" sort="Eich, Hans Theodor" uniqKey="Eich H" first="Hans Theodor" last="Eich">Hans Theodor Eich</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Radiotherapy, University Hospital of Muenster, Muenster</wicri:regionArea><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion><wicri:noRegion>Muenster</wicri:noRegion></affiliation></author><author><name sortKey="Schmezer, Peter" sort="Schmezer, Peter" uniqKey="Schmezer P" first="Peter" last="Schmezer">Peter Schmezer</name><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Division of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), Heidelberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Radiotherapy is a powerful cure for several types of solid tumours, but its application is often limited because of severe side effects in individual patients. With the aim to find biomarkers capable of predicting normal tissue side reactions we analysed the radiation responses of cells from individual head and neck tumour and breast cancer patients of different clinical radiosensitivity in a multicentric study. Multiple parameters of cellular radiosensitivity were analysed in coded samples of peripheral blood lymphocytes (PBLs) and derived lymphoblastoid cell lines (LCLs) from 15 clinical radio-hypersensitive tumour patients and compared to age- and sex-matched non-radiosensitive patient controls and 15 lymphoblastoid cell lines from age- and sex- matched healthy controls of the KORA study. Experimental parameters included ionizing radiation (IR)-induced cell death (AnnexinV), induction and repair of DNA strand breaks (Comet assay), induction of yH2AX foci (as a result of DNA double strand breaks), and whole genome expression analyses. Considerable inter-individual differences in IR-induced DNA strand breaks and their repair and/or cell death could be detected in primary and immortalised cells with the applied assays. The group of clinically radiosensitive patients was not unequivocally distinguishable from normal responding patients nor were individual overreacting patients in the test system unambiguously identified by two different laboratories. Thus, the <italic>in vitro</italic> test systems investigated here seem not to be appropriate for a general prediction of clinical reactions during or after radiotherapy due to the experimental variability compared to the small effect of radiation sensitivity. Genome-wide expression analysis however revealed a set of 67 marker genes which were differentially induced 6 h after in vitro-irradiation in lymphocytes from radio-hypersensitive and non-radiosensitive patients. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23110060</article-id><article-id pub-id-type="pmc">3479094</article-id><article-id pub-id-type="publisher-id">PONE-D-12-02102</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0047185</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Genetics</subject><subj-group><subject>Epigenetics</subject></subj-group></subj-group><subj-group><subject>Genomics</subject><subj-group><subject>Genome Expression Analysis</subject><subject>Genome Sequencing</subject></subj-group></subj-group><subj-group><subject>Immunology</subject><subj-group><subject>Immune Cells</subject><subj-group><subject>B Cells</subject><subject>T Cells</subject></subj-group></subj-group></subj-group><subj-group><subject>Radiobiology</subject></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject><subj-group><subject>Diagnostic Medicine</subject><subj-group><subject>Pathology</subject><subj-group><subject>General Pathology</subject><subj-group><subject>Biomarkers</subject></subj-group></subj-group></subj-group></subj-group><subj-group><subject>Oncology</subject><subj-group><subject>Cancer Treatment</subject><subj-group><subject>Radiation Therapy</subject></subj-group></subj-group><subj-group><subject>Radiotherapy</subject></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Evaluation of Different Biomarkers to Predict Individual Radiosensitivity in an Inter-Laboratory Comparison–Lessons for Future Studies</article-title><alt-title alt-title-type="running-head">Prediction of Individual Radiosensitivity</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Greve</surname><given-names>Burkhard</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bölling</surname><given-names>Tobias</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Amler</surname><given-names>Susanne</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rössler</surname><given-names>Ute</given-names></name><xref ref-type="aff" rid="aff8"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gomolka</surname><given-names>Maria</given-names></name><xref ref-type="aff" rid="aff8"><sup>8</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mayer</surname><given-names>Claudia</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Popanda</surname><given-names>Odilia</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dreffke</surname><given-names>Kristin</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="author-notes" rid="fn1"><sup>¤a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rickinger</surname><given-names>Astrid</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fritz</surname><given-names>Eberhard</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="author-notes" rid="fn2"><sup>¤b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Eckardt-Schupp</surname><given-names>Friederike</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sauerland</surname><given-names>Christina</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Braselmann</surname><given-names>Herbert</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sauter</surname><given-names>Wiebke</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Illig</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Riesenbeck</surname><given-names>Dorothea</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="fn3"><sup>¤c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Könemann</surname><given-names>Stefan</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="fn4"><sup>¤d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Willich</surname><given-names>Normann</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mörtl</surname><given-names>Simone</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Eich</surname><given-names>Hans Theodor</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Schmezer</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI), Jena, Germany</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Institute of Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></aff><aff id="aff4"><label>4</label><addr-line>Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany</addr-line></aff><aff id="aff5"><label>5</label><addr-line>Institute of Molecular Radiation Biology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></aff><aff id="aff6"><label>6</label><addr-line>Institute of Epidemiology, Helmholtz Centre Munich – German Research Centre for Environmental Health, Neuherberg, Germany</addr-line></aff><aff id="aff7"><label>7</label><addr-line>Division of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), Heidelberg, Germany</addr-line></aff><aff id="aff8"><label>8</label><addr-line>Federal Office for Radiation Protection, Department of Radiation Protection and Health, Oberschleissheim, Germany</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Chuang</surname><given-names>Eric Y.</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>National Taiwan University, Taiwan</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>greveb@uni-muenster.de</email></corresp><fn fn-type="conflict"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: BG TB SA NW PS MG EF FES. Performed the experiments: BG TB UR MG CM KD AR EF FES WS TI SM PS DR. Analyzed the data: BG TB SA UR DR CM OP KD AR EF FES CS HB WS NW SM PS. Contributed reagents/materials/analysis tools: BG NW HTE PS EF FES MG. Wrote the paper: BG SA UR MG OP EF FES WS DR SK HTE PS SM.</p></fn><fn id="fn1" fn-type="current-aff"><label>¤a</label><p>Current address: Institute of Radiobiology and Molecular Radiation Oncology, Philipps-University of Marburg, Marburg, Germany</p></fn><fn id="fn2" fn-type="current-aff"><label>¤b</label><p>Current address: Max-Planck-Institute for Biogeochemistry, Jena, Germany</p></fn><fn id="fn3" fn-type="current-aff"><label>¤c</label><p>Current address: Practice of Radiotherapy, Recklinghausen, Germany</p></fn><fn id="fn4" fn-type="current-aff"><label>¤d</label><p>Current address: Centre for Radiotherapy, Bochum, Germany</p></fn></author-notes><pub-date pub-type="collection"><year>2012</year></pub-date><pub-date pub-type="epub"><day>23</day><month>10</month><year>2012</year></pub-date><volume>7</volume><issue>10</issue><elocation-id>e47185</elocation-id><history><date date-type="received"><day>20</day><month>1</month><year>2012</year></date><date date-type="accepted"><day>12</day><month>9</month><year>2012</year></date></history><permissions><copyright-year>2012</copyright-year><copyright-holder>Greve et al</copyright-holder><license><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><p>Radiotherapy is a powerful cure for several types of solid tumours, but its application is often limited because of severe side effects in individual patients. With the aim to find biomarkers capable of predicting normal tissue side reactions we analysed the radiation responses of cells from individual head and neck tumour and breast cancer patients of different clinical radiosensitivity in a multicentric study. Multiple parameters of cellular radiosensitivity were analysed in coded samples of peripheral blood lymphocytes (PBLs) and derived lymphoblastoid cell lines (LCLs) from 15 clinical radio-hypersensitive tumour patients and compared to age- and sex-matched non-radiosensitive patient controls and 15 lymphoblastoid cell lines from age- and sex- matched healthy controls of the KORA study. Experimental parameters included ionizing radiation (IR)-induced cell death (AnnexinV), induction and repair of DNA strand breaks (Comet assay), induction of yH2AX foci (as a result of DNA double strand breaks), and whole genome expression analyses. Considerable inter-individual differences in IR-induced DNA strand breaks and their repair and/or cell death could be detected in primary and immortalised cells with the applied assays. The group of clinically radiosensitive patients was not unequivocally distinguishable from normal responding patients nor were individual overreacting patients in the test system unambiguously identified by two different laboratories. Thus, the <italic>in vitro</italic> test systems investigated here seem not to be appropriate for a general prediction of clinical reactions during or after radiotherapy due to the experimental variability compared to the small effect of radiation sensitivity. Genome-wide expression analysis however revealed a set of 67 marker genes which were differentially induced 6 h after in vitro-irradiation in lymphocytes from radio-hypersensitive and non-radiosensitive patients. These results warrant future validation in larger cohorts in order to determine parameters potentially predictive for clinical radiosensitivity.</p></abstract><funding-group><funding-statement>The project was financed by the Federal Ministry for the Environment, Nature Conservation and Nuclear safety (StSch 4467). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="12"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Allemagne</li></country><region><li>Bade-Wurtemberg</li><li>District de Karlsruhe</li></region><settlement><li>Heidelberg</li></settlement></list><tree><country name="Allemagne"><noRegion><name sortKey="Greve, Burkhard" sort="Greve, Burkhard" uniqKey="Greve B" first="Burkhard" last="Greve">Burkhard Greve</name></noRegion><name sortKey="Amler, Susanne" sort="Amler, Susanne" uniqKey="Amler S" first="Susanne" last="Amler">Susanne Amler</name><name sortKey="Bolling, Tobias" sort="Bolling, Tobias" uniqKey="Bolling T" first="Tobias" last="Bölling">Tobias Bölling</name><name sortKey="Braselmann, Herbert" sort="Braselmann, Herbert" uniqKey="Braselmann H" first="Herbert" last="Braselmann">Herbert Braselmann</name><name sortKey="Dreffke, Kristin" sort="Dreffke, Kristin" uniqKey="Dreffke K" first="Kristin" last="Dreffke">Kristin Dreffke</name><name sortKey="Eckardt Schupp, Friederike" sort="Eckardt Schupp, Friederike" uniqKey="Eckardt Schupp F" first="Friederike" last="Eckardt-Schupp">Friederike Eckardt-Schupp</name><name sortKey="Eich, Hans Theodor" sort="Eich, Hans Theodor" uniqKey="Eich H" first="Hans Theodor" last="Eich">Hans Theodor Eich</name><name sortKey="Fritz, Eberhard" sort="Fritz, Eberhard" uniqKey="Fritz E" first="Eberhard" last="Fritz">Eberhard Fritz</name><name sortKey="Gomolka, Maria" sort="Gomolka, Maria" uniqKey="Gomolka M" first="Maria" last="Gomolka">Maria Gomolka</name><name sortKey="Illig, Thomas" sort="Illig, Thomas" uniqKey="Illig T" first="Thomas" last="Illig">Thomas Illig</name><name sortKey="Konemann, Stefan" sort="Konemann, Stefan" uniqKey="Konemann S" first="Stefan" last="Könemann">Stefan Könemann</name><name sortKey="Mayer, Claudia" sort="Mayer, Claudia" uniqKey="Mayer C" first="Claudia" last="Mayer">Claudia Mayer</name><name sortKey="Mortl, Simone" sort="Mortl, Simone" uniqKey="Mortl S" first="Simone" last="Mörtl">Simone Mörtl</name><name sortKey="Popanda, Odilia" sort="Popanda, Odilia" uniqKey="Popanda O" first="Odilia" last="Popanda">Odilia Popanda</name><name sortKey="Rickinger, Astrid" sort="Rickinger, Astrid" uniqKey="Rickinger A" first="Astrid" last="Rickinger">Astrid Rickinger</name><name sortKey="Riesenbeck, Dorothea" sort="Riesenbeck, Dorothea" uniqKey="Riesenbeck D" first="Dorothea" last="Riesenbeck">Dorothea Riesenbeck</name><name sortKey="Rossler, Ute" sort="Rossler, Ute" uniqKey="Rossler U" first="Ute" last="Rössler">Ute Rössler</name><name sortKey="Sauerland, Christina" sort="Sauerland, Christina" uniqKey="Sauerland C" first="Christina" last="Sauerland">Christina Sauerland</name><name sortKey="Sauter, Wiebke" sort="Sauter, Wiebke" uniqKey="Sauter W" first="Wiebke" last="Sauter">Wiebke Sauter</name><name sortKey="Schmezer, Peter" sort="Schmezer, Peter" uniqKey="Schmezer P" first="Peter" last="Schmezer">Peter Schmezer</name><name sortKey="Willich, Normann" sort="Willich, Normann" uniqKey="Willich N" first="Normann" last="Willich">Normann Willich</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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