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

被引：0

作者：

Bratic Hench, Ivana ^{[1
]}

Roma, Luca ^{[1
]}

Conticelli, Floriana ^{[1
,2
]}

Bubendorf, Lenard ^{[1
]}

Calgua, Byron ^{[1
]}

Le Magnen, Clementine ^{[1
,3
,4
]}

Piscuoglio, Salvatore ^{[1
,4
]}

Rubin, Mark A. ^{[5
,6
]}

Chirindel, Alin ^{[7
]}

Nicolas, Guillaume P. ^{[7
]}

Vlajnic, Tatjana ^{[1
]}

Zellweger, Tobias ^{[8
]}

Templeton, Arnoud J. ^{[8
,9
,10
]}

Stenner, Frank ^{[11
]}

Ruiz, Christian ^{[1
]}

Rentsch, Cyrill ^{[3
]}

Bubendorf, Lukas ^{[1
]}

Wong, David

机构：

[1] Univ Basel, Univ Hosp Basel, Inst Med Genet & Pathol, CH-4031 Basel, Switzerland

[2] Univ Naples Federico II, Dept Publ Hlth, I-80131 Naples, Italy

[3] Univ Basel, Univ Hosp Basel, Dept Urol, CH-4031 Basel, Switzerland

[4] Univ Basel, Univ Hosp Basel, Dept Biomed, CH-4031 Basel, Switzerland

[5] Bern Ctr Precis Med, Dept Biomed Res, Precis Oncol Lab, CH-3008 Bern, Switzerland

[6] Univ Bern, Bern Univ Hosp, Bern Ctr Precis Med, Inselspital, CH-3008 Bern, Switzerland

[7] Univ Hosp Basel, Dept Theragnost, Div Nucl Med, CH-4031 Basel, Switzerland

[8] St Clara Hosp, CH-4058 Basel, Switzerland

[9] St Clara Res, Basel, Switzerland

[10] Univ Basel, Fac Med, CH-4058 Basel, Switzerland

[11] Univ Hosp Basel, Div Oncol, CH-4031 Basel, Switzerland

来源：

CANCERS | 2024年 / 16卷 / 01期

关键词：

prostate cancer; liquid biopsy; precision medicine; circulating cell-free DNA; next-generation sequencing; RESISTANCE; MUTATIONS; THERAPY;

D O I：

10.3390/cancers16010045

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary Prostate cancer (PCa) accounts for the second-highest mortality rate in cancer-associated deaths. Liquid biopsy has great potential to tailor treatment choices in advanced PCa. In this study, we evaluated the utility and diagnostic potential of a custom-designed NGS cfDNA panel based on the AmpliSeq HD Technology in advanced PCa. cfDNA somatic mutations were detected in the majority (71%) of examined advanced PCa patients. The most frequently mutated genes in the PCa cohort of 68 patients (40 metastatic castration-resistant and 28 metastatic hormone-naive PCa) were: TP53, FOXA1, SPOP, PTEN, AR, CTNNB1, RB1, and PIK3CA. AR amplifications were detected in 31% of mCRPC patients. This approach appears to be a straightforward and cost-effective method for detecting clinically relevant somatic mutations in cfDNA to aid in clinical decision-making.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.

引用

页数：16

共 44 条

[1] Genomic correlates of clinical outcome in advanced prostate cancer [J].

Abida, Wassim ;

Cyrta, Joanna ;

Heller, Glenn ;

Prandi, Davide ;

Armenia, Joshua ;

Coleman, Ilsa ;

Cieslik, Marcin ;

Benelli, Matteo ;

Robinson, Dan ;

Van Allen, Eliezer M. ;

Sboner, Andrea ;

Fedrizzi, Tarcisio ;

Mosquera, Juan Miguel ;

Robinson, Brian D. ;

De Sarkar, Navonil ;

Kunju, Lakshmi P. ;

Tomlins, Scott ;

Wu, Yi Mi ;

Rodrigues, Daniel Nava ;

Loda, Massimo ;

Gopalan, Anuradha ;

Reuter, Victor E. ;

Pritchard, Colin C. ;

Mateo, Joaquin ;

Bianchini, Diletta ;

Miranda, Susana ;

Carreira, Suzanne ;

Rescigno, Pasquale ;

Filipenko, Julie ;

Vinson, Jacob ;

Montgomery, Robert B. ;

Beltran, Himisha ;

Heath, Elisabeth I. ;

Scher, Howard I. ;

Kantoff, Philip W. ;

Taplin, Mary-Ellen ;

Schultz, Nikolaus ;

deBono, Johann S. ;

Demichelis, Francesca ;

Nelson, Peter S. ;

Rubin, Mark A. ;

Chinnaiyan, Arul M. ;

Sawyers, Charles L. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (23) :11428-11436

[2] Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study [J].

Aggarwal, Rahul ;

Huang, Jiaoti ;

Alumkal, Joshi J. ;

Zhang, Li ;

Feng, Felix Y. ;

Thomas, George V. ;

Weinstein, Alana S. ;

Friedl, Verena ;

Zhang, Can ;

Witte, Owen N. ;

Lloyd, Paul ;

Gleave, Martin ;

Evans, Christopher P. ;

Youngren, Jack ;

Beer, Tomasz M. ;

Rettig, Matthew ;

Wong, Christopher K. ;

True, Lawrence ;

Foye, Adam ;

Playdle, Denise ;

Ryan, Charles J. ;

Lara, Primo ;

Chi, Kim N. ;

Uzunangelov, Vlado ;

Sokolov, Artem ;

Newton, Yulia ;

Beltran, Himisha ;

Demichelis, Francesca ;

Rubin, Mark A. ;

Stuart, Joshua M. ;

Small, Eric J. .

JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (24) :2492-+

[3] Circulating Tumor DNA Genomics Correlate with Resistance to Abiraterone and Enzalutamide in Prostate Cancer [J].

Annala, Matti ;

Vandekerkhove, Gillian ;

Khalaf, Daniel ;

Taavitsainen, Sinja ;

Beja, Kevin ;

Warner, Evan W. ;

Sunderland, Katherine ;

Kollmannsberger, Christian ;

Eigl, Bernhard J. ;

Finch, Daygen ;

Oja, Conrad D. ;

Vergidis, Joanna ;

Zulfiqar, Muhammad ;

Azad, Arun A. ;

Nykter, Matti ;

Gleave, Martin E. ;

Wyatt, Alexander W. ;

Chi, Kim N. .

CANCER DISCOVERY, 2018, 8 (04) :444-457

[4] Clinical and pathological features associated with circulating tumor DNA content in real-world patients with metastatic prostate cancer [J].

Antonarakis, Emmanuel S. ;

Tierno, Marni ;

Fisher, Virginia ;

Tukachinsky, Hanna ;

Alexander, Sonja ;

Hamdani, Omar ;

Hiemenz, Matthew C. ;

Huang, Richard S. P. ;

Oxnard, Geoffrey R. ;

Graf, Ryon P. .

PROSTATE, 2022, 82 (07) :867-875

[5] The long tail of oncogenic drivers in prostate cancer [J].

Armenia, Joshua ;

Wankowicz, Stephanie A. M. ;

Liu, David ;

Gao, Jianjiong ;

Kundra, Ritika ;

Reznik, Ed ;

Chatila, Walid K. ;

Chakravarty, Debyani ;

Han, G. Celine ;

Coleman, Ilsa ;

Montgomery, Bruce ;

Pritchard, Colin ;

Morrissey, Colm ;

Barbieri, Christopher E. ;

Beltran, Himisha ;

Sboner, Andrea ;

Zafeiriou, Zafeiris ;

Miranda, Susana ;

Bielski, Craig M. ;

Penson, Alexander V. ;

Tolonen, Charlotte ;

Huang, Franklin W. ;

Robinson, Dan ;

Wu, Yi Mi ;

Lonigro, Robert ;

Garraway, Levi A. ;

Demichelis, Francesca ;

Kantoff, Philip W. ;

Taplin, Mary-Ellen ;

Abida, Wassim ;

Taylor, Barry S. ;

Scher, Howard I. ;

Nelson, Peter S. ;

de Bono, Johann S. ;

Rubin, Mark A. ;

Sawyers, Charles L. ;

Chinnaiyan, Arul M. ;

Schultz, Nikolaus ;

Van Allen, Eliezer M. .

NATURE GENETICS, 2018, 50 (05) :645-+

[6] Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies [J].

Bettegowda, Chetan ;

Sausen, Mark ;

Leary, Rebecca J. ;

Kinde, Isaac ;

Wang, Yuxuan ;

Agrawal, Nishant ;

Bartlett, Bjarne R. ;

Wang, Hao ;

Luber, Brandon ;

Alani, Rhoda M. ;

Antonarakis, Emmanuel S. ;

Azad, Nilofer S. ;

Bardelli, Alberto ;

Brem, Henry ;

Cameron, John L. ;

Lee, Clarence C. ;

Fecher, Leslie A. ;

Gallia, Gary L. ;

Gibbs, Peter ;

Le, Dung ;

Giuntoli, Robert L. ;

Goggins, Michael ;

Hogarty, Michael D. ;

Holdhoff, Matthias ;

Hong, Seung-Mo ;

Jiao, Yuchen ;

Juhl, Hartmut H. ;

Kim, Jenny J. ;

Siravegna, Giulia ;

Laheru, Daniel A. ;

Lauricella, Calogero ;

Lim, Michael ;

Lipson, Evan J. ;

Marie, Suely Kazue Nagahashi ;

Netto, George J. ;

Oliner, Kelly S. ;

Olivi, Alessandro ;

Olsson, Louise ;

Riggins, Gregory J. ;

Sartore-Bianchi, Andrea ;

Schmidt, Kerstin ;

Shih, Ie-Ming ;

Oba-Shinjo, Sueli Mieko ;

Siena, Salvatore ;

Theodorescu, Dan ;

Tie, Jeanne ;

Harkins, Timothy T. ;

Veronese, Silvio ;

Wang, Tian-Li ;

Weingart, Jon D. .

SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (224)

[7] Clonal Hematopoiesis in Liquid Biopsy: From Biological Noise to Valuable Clinical Implications [J].

Chan, Hiu Ting ;

Chin, Yoon Ming ;

Nakamura, Yusuke ;

Low, Siew-Kee .

CANCERS, 2020, 12 (08) :1-18

[8] Baseline Plasma Tumor DNA (ctDNA) Correlates with PSA Kinetics in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide [J].

Conteduca, Vincenza ;

Casadei, Chiara ;

Scarpi, Emanuela ;

Brighi, Nicole ;

Schepisi, Giuseppe ;

Lolli, Cristian ;

Gurioli, Giorgia ;

Toma, Ilaria ;

Poti, Giulia ;

Farolfi, Alberto ;

De Giorgi, Ugo .

CANCERS, 2022, 14 (09)

[9] The evolving landscape of prostate cancer somatic mutations [J].

Cotter, Kellie ;

Rubin, Mark A. .

PROSTATE, 2022, 82 :S13-S24

[10] Liquid Biopsy in Prostate Cancer Management-Current Challenges and Future Perspectives [J].

Crocetto, Felice ;

Russo, Gianluca ;

Di Zazzo, Erika ;

Pisapia, Pasquale ;

Mirto, Benito Fabio ;

Palmieri, Alessandro ;

Pepe, Francesco ;

Bellevicine, Claudio ;

Russo, Alessandro ;

La Civita, Evelina ;

Terracciano, Daniela ;

Malapelle, Umberto ;

Troncone, Giancarlo ;

Barone, Biagio .

CANCERS, 2022, 14 (13)

← 1 2 3 4 5 →