Biomarkers of Castrate Resistance in Prostate Cancer: Androgen Receptor Amplification and T877A Mutation Detection by Multiplex Droplet Digital PCR
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...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/1/257 |
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| author | Francis P. Young Therese M. Becker Mohammed Nimir Thomas Opperman Wei Chua Bavanthi Balakrishnar Paul de Souza Yafeng Ma |
| author_facet | Francis P. Young Therese M. Becker Mohammed Nimir Thomas Opperman Wei Chua Bavanthi Balakrishnar Paul de Souza Yafeng Ma |
| author_sort | Francis P. Young |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T03:35:38Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T03:35:38Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-59eb50ad7c57461683256eec9faf22662023-11-23T11:46:08ZengMDPI AGJournal of Clinical Medicine2077-03832022-01-0111125710.3390/jcm11010257Biomarkers of Castrate Resistance in Prostate Cancer: Androgen Receptor Amplification and T877A Mutation Detection by Multiplex Droplet Digital PCRFrancis P. Young0Therese M. Becker1Mohammed Nimir2Thomas Opperman3Wei Chua4Bavanthi Balakrishnar5Paul de Souza6Yafeng Ma7Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, AustraliaCentre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, AustraliaCentre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, AustraliaCentre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, AustraliaSchool of Medicine, Western Sydney University, Campbelltown, NSW 2560, AustraliaLiverpool Hospital, Liverpool, NSW 2170, AustraliaSouth Western Clinical School, University of New South Wales, Liverpool, NSW 2170, AustraliaCentre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, AustraliaAndrogen 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.https://www.mdpi.com/2077-0383/11/1/257prostate cancercell free DNAliquid biopsyandrogen receptormutationamplification |
| spellingShingle | Francis P. Young Therese M. Becker Mohammed Nimir Thomas Opperman Wei Chua Bavanthi Balakrishnar Paul de Souza Yafeng Ma Biomarkers of Castrate Resistance in Prostate Cancer: Androgen Receptor Amplification and T877A Mutation Detection by Multiplex Droplet Digital PCR Journal of Clinical Medicine prostate cancer cell free DNA liquid biopsy androgen receptor mutation amplification |
| title | Biomarkers of Castrate Resistance in Prostate Cancer: Androgen Receptor Amplification and T877A Mutation Detection by Multiplex Droplet Digital PCR |
| title_full | Biomarkers of Castrate Resistance in Prostate Cancer: Androgen Receptor Amplification and T877A Mutation Detection by Multiplex Droplet Digital PCR |
| title_fullStr | Biomarkers of Castrate Resistance in Prostate Cancer: Androgen Receptor Amplification and T877A Mutation Detection by Multiplex Droplet Digital PCR |
| title_full_unstemmed | Biomarkers of Castrate Resistance in Prostate Cancer: Androgen Receptor Amplification and T877A Mutation Detection by Multiplex Droplet Digital PCR |
| title_short | Biomarkers of Castrate Resistance in Prostate Cancer: Androgen Receptor Amplification and T877A Mutation Detection by Multiplex Droplet Digital PCR |
| title_sort | biomarkers of castrate resistance in prostate cancer androgen receptor amplification and t877a mutation detection by multiplex droplet digital pcr |
| topic | prostate cancer cell free DNA liquid biopsy androgen receptor mutation amplification |
| url | https://www.mdpi.com/2077-0383/11/1/257 |
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