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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Published in:Biomedicines 2023-03, Vol.11 (3), p.761
Main Authors: Januskevicius, Tomas, Sabaliauskaite, Rasa, Dabkeviciene, Daiva, Vaicekauskaite, Ieva, Kulikiene, Ilona, Sestokaite, Agne, Vidrinskaite, Asta, Bakavicius, Arnas, Jankevicius, Feliksas, Ulys, Albertas, Jarmalaite, Sonata
Format: Article
Language:English
Subjects:
abiraterone acetate
Acetic acid
Androgens
Biopsy
BRCA1 protein
BRCA1/BRCA2 genes
BRCA2 protein
Cancer therapies
Castration
castration-resistant prostate cancer
Chemotherapy
Deoxyribonucleic acid
DNA
DNA damage
DNA damage repair
DNA sequencing
Genes
Genetic screening
Genomics
Leukocytes
Medical prognosis
Metastases
Metastasis
Methods
Mutation
Nucleotide sequencing
Prostate cancer
Radium
Sediments
Urine
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Summary:(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. , , and mutations were associated with significantly shorter PFS in response to conventional androgen deprivation therapy and first-line mCRPC therapy with abiraterone acetate. Additionally, and 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.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines11030761