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However, the relationship between ctDNA abundance, detectable somatic genomic alterations and clinical progression of mCRPC remains unexplored. Our study aimed to investigate changes in plasma DNA during disease progression and their associations with clinical variables in mCRPC patients. We analyzed ctDNA in two cohorts including 94 plasma samples from 25 treatment courses (23 patients) and 334 plasma samples from 125 patients, respectively. We conducted whole\u2010genome sequencing (plasma\u2010Seq) for genome\u2010wide profiling of somatic copy number alterations and targeted sequencing of 31 prostate cancer\u2010associated genes. The combination of plasma\u2010Seq with targeted<jats:italic>AR<\/jats:italic>analyses identified prostate cancer\u2010related genomic alterations in 16 of 25 (64%) treatment courses in the first cohort, in which we demonstrated that<jats:italic>AR<\/jats:italic>amplification does not always correlate with poor abiraterone and enzalutamide therapy outcome. As we observed a wide variability of ctDNA levels, we evaluated ctDNA levels and their association with clinical parameters and included the second, larger cohort for these analyses. Employing altogether 428 longitudinal plasma samples from 148 patients, we identified the presence of bone metastases, increased lactate dehydrogenase and prostate\u2010specific antigen (PSA) as having the strongest association with high ctDNA levels. In summary, ctDNA alterations are observable in the majority of patients with mCRPC and may eventually be useful to guide clinical decision\u2010making in this setting.<\/jats:p>","DOI":"10.1002\/ijc.31397","type":"journal-article","created":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T15:08:19Z","timestamp":1521990499000},"page":"1236-1248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Genomic alterations in plasma DNA from patients with metastasized prostate cancer receiving abiraterone or enzalutamide"],"prefix":"10.1002","volume":"143","author":[{"given":"Jelena","family":"Belic","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, Neue Stiftingtalstra\u00dfe 6 A\u20108010 Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricarda","family":"Graf","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, Neue Stiftingtalstra\u00dfe 6 A\u20108010 Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bauernhofer","sequence":"additional","affiliation":[{"name":"Division of Oncology Medical University of Graz, Auenbruggerplatz 15 A\u20108036 Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yauheniya","family":"Cherkas","sequence":"additional","affiliation":[{"name":"Pharmaceutical Companies of Johnson &amp; Johnson Janssen Oncology Therapeutic Area, Janssen Research and Development, LLC Spring House PA 19477 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5941-1160","authenticated-orcid":false,"given":"Peter","family":"Ulz","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, Neue Stiftingtalstra\u00dfe 6 A\u20108010 Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Waldispuehl\u2010Geigl","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, Neue Stiftingtalstra\u00dfe 6 A\u20108010 Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Perakis","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, Neue Stiftingtalstra\u00dfe 6 A\u20108010 Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gormley","sequence":"additional","affiliation":[{"name":"Pharmaceutical Companies of Johnson &amp; Johnson Janssen Oncology Therapeutic Area, Janssen Research and Development, LLC Spring House PA 19477 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaymala","family":"Patel","sequence":"additional","affiliation":[{"name":"Pharmaceutical Companies of Johnson &amp; Johnson Janssen Oncology Therapeutic Area, Janssen Research and Development, LLC Spring House PA 19477 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"Li","sequence":"additional","affiliation":[{"name":"Pharmaceutical Companies of Johnson &amp; Johnson Janssen Oncology Therapeutic Area, Janssen Research and Development, LLC Spring House PA 19477 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen B.","family":"Geigl","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, Neue Stiftingtalstra\u00dfe 6 A\u20108010 Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Smirnov","sequence":"additional","affiliation":[{"name":"Pharmaceutical Companies of Johnson &amp; Johnson Janssen Oncology Therapeutic Area, Janssen Research and Development, LLC Spring House PA 19477 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Heitzer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, Neue Stiftingtalstra\u00dfe 6 A\u20108010 Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell","family":"Gross","sequence":"additional","affiliation":[{"name":"Lawrence J. 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