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Urinary DNA as a Tool for Germline and Somatic Mutation Detection in Castration-Resistant Prostate Cancer Patients
(1) Background: DNA damage response (DDR) pathway gene mutations are detectable in a significant number of patients with metastatic castration-resistant prostate cancer (mCRPC). The study aimed at identification of germline and/or somatic DDR mutations in blood and urine samples from patients with m...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10044986/ https://www.ncbi.nlm.nih.gov/pubmed/36979741 http://dx.doi.org/10.3390/biomedicines11030761 |
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author | Januskevicius, Tomas Sabaliauskaite, Rasa Dabkeviciene, Daiva Vaicekauskaite, Ieva Kulikiene, Ilona Sestokaite, Agne Vidrinskaite, Asta Bakavicius, Arnas Jankevicius, Feliksas Ulys, Albertas Jarmalaite, Sonata |
author_facet | Januskevicius, Tomas Sabaliauskaite, Rasa Dabkeviciene, Daiva Vaicekauskaite, Ieva Kulikiene, Ilona Sestokaite, Agne Vidrinskaite, Asta Bakavicius, Arnas Jankevicius, Feliksas Ulys, Albertas Jarmalaite, Sonata |
author_sort | Januskevicius, Tomas |
collection | PubMed |
description | (1) Background: DNA damage response (DDR) pathway gene mutations are detectable in a significant number of patients with metastatic castration-resistant prostate cancer (mCRPC). The study aimed at identification of germline and/or somatic DDR mutations in blood and urine samples from patients with mCRPC for correlation with responses to entire sequence of systemic treatment and survival outcomes. (2) Methods: DDR gene mutations were assessed prospectively in DNA samples from leukocytes and urine sediments from 149 mCRPC patients using five-gene panel targeted sequencing. The impact of DDR status on progression-free survival, as well as treatment-specific and overall survival, was evaluated using Kaplan–Meier curves and Cox regression. (3) Results: DDR mutations were detected in 16.6% of urine and 15.4% of blood samples. BRCA1, BRCA2, CHEK2, ATM and NBN mutations were associated with significantly shorter PFS in response to conventional androgen deprivation therapy and first-line mCRPC therapy with abiraterone acetate. Additionally, BRCA1 and BRCA2 mutation-bearing patients had a significantly worse response to radium-223. However, DDR mutation status was predictive for the favourable effect of second-line abiraterone acetate after previous taxane-based chemotherapy. (4) Conclusions: Our data confirm the benefit of non-invasive urine-based genetic testing for timely identification of high-risk prostate cancer cases for treatment personalization. |
format | Online Article Text |
id | pubmed-10044986 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100449862023-03-29 Urinary DNA as a Tool for Germline and Somatic Mutation Detection in Castration-Resistant Prostate Cancer Patients Januskevicius, Tomas Sabaliauskaite, Rasa Dabkeviciene, Daiva Vaicekauskaite, Ieva Kulikiene, Ilona Sestokaite, Agne Vidrinskaite, Asta Bakavicius, Arnas Jankevicius, Feliksas Ulys, Albertas Jarmalaite, Sonata Biomedicines Article (1) Background: DNA damage response (DDR) pathway gene mutations are detectable in a significant number of patients with metastatic castration-resistant prostate cancer (mCRPC). The study aimed at identification of germline and/or somatic DDR mutations in blood and urine samples from patients with mCRPC for correlation with responses to entire sequence of systemic treatment and survival outcomes. (2) Methods: DDR gene mutations were assessed prospectively in DNA samples from leukocytes and urine sediments from 149 mCRPC patients using five-gene panel targeted sequencing. The impact of DDR status on progression-free survival, as well as treatment-specific and overall survival, was evaluated using Kaplan–Meier curves and Cox regression. (3) Results: DDR mutations were detected in 16.6% of urine and 15.4% of blood samples. BRCA1, BRCA2, CHEK2, ATM and NBN mutations were associated with significantly shorter PFS in response to conventional androgen deprivation therapy and first-line mCRPC therapy with abiraterone acetate. Additionally, BRCA1 and BRCA2 mutation-bearing patients had a significantly worse response to radium-223. However, DDR mutation status was predictive for the favourable effect of second-line abiraterone acetate after previous taxane-based chemotherapy. (4) Conclusions: Our data confirm the benefit of non-invasive urine-based genetic testing for timely identification of high-risk prostate cancer cases for treatment personalization. MDPI 2023-03-02 /pmc/articles/PMC10044986/ /pubmed/36979741 http://dx.doi.org/10.3390/biomedicines11030761 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Januskevicius, Tomas Sabaliauskaite, Rasa Dabkeviciene, Daiva Vaicekauskaite, Ieva Kulikiene, Ilona Sestokaite, Agne Vidrinskaite, Asta Bakavicius, Arnas Jankevicius, Feliksas Ulys, Albertas Jarmalaite, Sonata Urinary DNA as a Tool for Germline and Somatic Mutation Detection in Castration-Resistant Prostate Cancer Patients |
title | Urinary DNA as a Tool for Germline and Somatic Mutation Detection in Castration-Resistant Prostate Cancer Patients |
title_full | Urinary DNA as a Tool for Germline and Somatic Mutation Detection in Castration-Resistant Prostate Cancer Patients |
title_fullStr | Urinary DNA as a Tool for Germline and Somatic Mutation Detection in Castration-Resistant Prostate Cancer Patients |
title_full_unstemmed | Urinary DNA as a Tool for Germline and Somatic Mutation Detection in Castration-Resistant Prostate Cancer Patients |
title_short | Urinary DNA as a Tool for Germline and Somatic Mutation Detection in Castration-Resistant Prostate Cancer Patients |
title_sort | urinary dna as a tool for germline and somatic mutation detection in castration-resistant prostate cancer patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10044986/ https://www.ncbi.nlm.nih.gov/pubmed/36979741 http://dx.doi.org/10.3390/biomedicines11030761 |
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