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

doi:10.3390/cancers16010045

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

Cancers (Basel). 2023 Dec 21;16(1):45. doi: 10.3390/cancers16010045.

Authors

Ivana Bratic Hench¹, Luca Roma¹, Floriana Conticelli^{1

2}, Lenard Bubendorf¹, Byron Calgua¹, Clémentine Le Magnen^{1

3

4}, Salvatore Piscuoglio^{1

4}, Mark A Rubin^{5

6}, Alin Chirindel⁷, Guillaume P Nicolas⁷, Tatjana Vlajnic¹, Tobias Zellweger⁸, Arnoud J Templeton^{8

9}, Frank Stenner¹⁰, Christian Ruiz¹, Cyrill Rentsch³, Lukas Bubendorf¹

Affiliations

¹ Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
² Department of Public Health, University of Naples Federico II, 80131 Naples, Italy.
³ Department of Urology, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
⁴ Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
⁵ Precision Oncology Laboratory, Department for Biomedical Research, Bern Center for Precision Medicine, 3008 Bern, Switzerland.
⁶ Bern Center for Precision Medicine, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, Switzerland.
⁷ Division of Nuclear Medicine, Department of Theragnostics, University Hospital Basel, 4031 Basel, Switzerland.
⁸ St. Claraspital, 4058 Basel, Switzerland.
⁹ St. Clara Research, Basel and Faculty of Medicine, University Basel, 4058 Basel, Switzerland.
¹⁰ Division of Oncology, University Hospital Basel, 4031 Basel, Switzerland.

Abstract

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.

Keywords: circulating cell-free DNA; liquid biopsy; next-generation sequencing; precision medicine; prostate cancer.

Grants and funding

Krebsliga beider Basel (KLbB-5073-02-2020) funded this project. The Swiss Cancer Research Foundation grants KFS-4982-02-2020 (M.A. Rubin) and KFS-4988-02-2020-R (S. Piscuoglio). The Prof. Dr. Max Cloëtta Foundation supports S. Piscuoglio. Dottorato PON 2014-2020 (Programma Operativo Nazionale) Ricerca ed Innovazione (Project code: DOT1318341) and Fondo Sociale Europeo, Azione I.1 “Dottorati Innovativi con caratterizzazione Industriale” via Ministero dell’ Istruzione, dell’Universita’ e della Ricerca funded Dr. Floriana Conticelli. Thermo Fisher Scientific (Waltham MA, USA) provided the sequencing reagents for this study.