DOI: 10.3390/cancers16010045 ISSN: 2072-6694

Cell-Free DNA Genomic Profiling and Its Clinical Implementation in Advanced Prostate Cancer

Ivana Bratic Hench, Luca Roma, Floriana Conticelli, Lenard Bubendorf, Byron Calgua, Clémentine Le Magnen, Salvatore Piscuoglio, Mark A. Rubin, Alin Chirindel, Guillaume P. Nicolas, Tatjana Vlajnic, Tobias Zellweger, Arnoud J. Templeton, Frank Stenner, Christian Ruiz, Cyrill Rentsch, Lukas Bubendorf
  • Cancer Research
  • Oncology

Most men with prostate cancer (PCa), despite potentially curable localized disease at initial diagnosis, progress to metastatic disease. Despite numerous treatment options, choosing the optimal treatment for individual patients remains challenging. Biomarkers guiding treatment sequences in an advanced setting are lacking. To estimate the diagnostic potential of liquid biopsies in guiding personalized treatment of PCa, we evaluated the utility of a custom-targeted next-generation sequencing (NGS) panel based on the AmpliSeq HD Technology. Ultra-deep sequencing on plasma circulating free DNA (cfDNA) samples of 40 metastatic castration-resistant PCa (mCRPC) and 28 metastatic hormone-naive PCa (mCSPC) was performed. CfDNA somatic mutations were detected in 48/68 (71%) patients. Of those 68 patients, 42 had matched tumor and cfDNA samples. In 21/42 (50%) patients, mutations from the primary tumor tissue were detected in the plasma cfDNA. In 7/42 (17%) patients, mutations found in the primary tumor were not detected in the cfDNA. Mutations from primary tumors were detected in all tested mCRPC patients (17/17), but only in 4/11 with mCSPC. AR amplifications were detected in 12/39 (31%) mCRPC patients. These results indicate that our targeted NGS approach has high sensitivity and specificity for detecting clinically relevant mutations in PCa.

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