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Article

Biomarkers of Castrate Resistance in Prostate Cancer: Androgen Receptor Amplification and T877A Mutation Detection by Multiplex Droplet Digital PCR

1
Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia
2
South Western Clinical School, University of New South Wales, Liverpool, NSW 2170, Australia
3
School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia
4
Liverpool Hospital, Liverpool, NSW 2170, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Laura Muinelo-Romay
J. Clin. Med. 2022, 11(1), 257; https://doi.org/10.3390/jcm11010257
Received: 11 November 2021 / Revised: 25 December 2021 / Accepted: 28 December 2021 / Published: 4 January 2022
Androgen Receptor (AR) alterations (amplification, point mutations, and splice variants) are master players in metastatic castration resistant prostate cancer (CRPC) progression and central therapeutic targets for patient management. Here, we have developed two multiplexed droplet digital PCR (ddPCR) assays to detect AR copy number (CN) and the key point mutation T877A. Overcoming challenges of determining gene amplification from liquid biopsies, these assays cross-validate each other to produce reliable AR amplification and mutation data from plasma cell free DNA (cfDNA) of advanced prostate cancer (PC) patients. Analyzing a mixed PC patient cohort consisting of CRPC and hormone sensitive prostate cancer (HSPC) patients showed that 19% (9/47) patients had AR CN amplification. As expected, only CRPC patients were positive for AR amplification, while interestingly the T877A mutation was identified in two patients still considered HSPC at the time. The ddPCR based analysis of AR alterations in cfDNA is highly economic, feasible, and informative to provide biomarker detection that may help to decide on the best follow-up therapy for CRPC patients. View Full-Text
Keywords: prostate cancer; cell free DNA; liquid biopsy; androgen receptor; mutation; amplification prostate cancer; cell free DNA; liquid biopsy; androgen receptor; mutation; amplification
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MDPI and ACS Style

Young, F.P.; Becker, T.M.; Nimir, M.; Opperman, T.; Chua, W.; Balakrishnar, B.; de Souza, P.; Ma, Y. Biomarkers of Castrate Resistance in Prostate Cancer: Androgen Receptor Amplification and T877A Mutation Detection by Multiplex Droplet Digital PCR. J. Clin. Med. 2022, 11, 257. https://doi.org/10.3390/jcm11010257

AMA Style

Young FP, Becker TM, Nimir M, Opperman T, Chua W, Balakrishnar B, de Souza P, Ma Y. Biomarkers of Castrate Resistance in Prostate Cancer: Androgen Receptor Amplification and T877A Mutation Detection by Multiplex Droplet Digital PCR. Journal of Clinical Medicine. 2022; 11(1):257. https://doi.org/10.3390/jcm11010257

Chicago/Turabian Style

Young, Francis P., Therese M. Becker, Mohammed Nimir, Thomas Opperman, Wei Chua, Bavanthi Balakrishnar, Paul de Souza, and Yafeng Ma. 2022. "Biomarkers of Castrate Resistance in Prostate Cancer: Androgen Receptor Amplification and T877A Mutation Detection by Multiplex Droplet Digital PCR" Journal of Clinical Medicine 11, no. 1: 257. https://doi.org/10.3390/jcm11010257

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