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Updated: Aug 5, 2025
Cell-Free DNA Integrity Analysis in Urine Samples
Published on: January 5, 2017
Urinary DNA as a Tool for Germline and Somatic Mutation Detection in Castration-Resistant Prostate Cancer Patients
Tomas Januskevicius1, Rasa Sabaliauskaite2, Daiva Dabkeviciene3
1Clinic of Gastroenterology, Nephro-Urology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, M. K. Ciurlionio st. 21/27, LT-03101 Vilnius, Lithuania.
Abstract:
(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.
Insights
Germline and somatic DNA damage response (DDR) gene mutations in metastatic castration-resistant prostate cancer (mCRPC) impact treatment response. Urine testing identifies high-risk patients for personalized therapy.
Area of Science:
- Oncology
- Genetics
- Urology
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) frequently harbors DNA damage response (DDR) pathway gene mutations.
- Identifying these mutations aids in understanding treatment resistance and patient stratification.
Purpose of the Study:
- To identify germline and/or somatic DDR mutations in blood and urine from mCRPC patients.
- To correlate DDR mutation status with responses to systemic treatments and survival outcomes.
Main Methods:
- Prospective assessment of DDR gene mutations in leukocytes and urine sediments from 149 mCRPC patients using a five-gene panel targeted sequencing.
- Evaluation of progression-free survival (PFS) and treatment-specific/overall survival using Kaplan-Meier curves and Cox regression.
Main Results:
- DDR mutations were found in 16.6% of urine and 15.4% of blood samples.
- Mutations in BRCA1, BRCA2, CHEK2, ATM, and NBN were linked to shorter PFS with standard androgen deprivation therapy and first-line abiraterone acetate.
- DDR mutations predicted a favorable response to second-line abiraterone acetate post-taxane chemotherapy.
Conclusions:
- Non-invasive urine-based genetic testing is beneficial for early identification of high-risk prostate cancer.
- This approach facilitates personalized treatment strategies for mCRPC patients.
