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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...

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Autores principales: Januskevicius, Tomas, Sabaliauskaite, Rasa, Dabkeviciene, Daiva, Vaicekauskaite, Ieva, Kulikiene, Ilona, Sestokaite, Agne, Vidrinskaite, Asta, Bakavicius, Arnas, Jankevicius, Feliksas, Ulys, Albertas, Jarmalaite, Sonata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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