Urinary DNA as a Tool for Germline and Somatic Mutation Detection in Castration-Resistant Prostate Cancer Patients
Tomas Januskevicius,
Rasa Sabaliauskaite,
Daiva Dabkeviciene,
Ieva Vaicekauskaite,
Ilona Kulikiene,
Agne Sestokaite,
Asta Vidrinskaite,
Arnas Bakavicius,
Feliksas Jankevicius,
Albertas Ulys,
Sonata Jarmalaite
Affiliations
Tomas Januskevicius
Clinic 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
Rasa Sabaliauskaite
Laboratory of Genetic Diagnostic, National Cancer Institute, Santariskiu st. 1, LT-08406 Vilnius, Lithuania
Daiva Dabkeviciene
Biobank, National Cancer Institute, Santariskiu st. 1, LT-08406 Vilnius, Lithuania
Ieva Vaicekauskaite
Laboratory of Genetic Diagnostic, National Cancer Institute, Santariskiu st. 1, LT-08406 Vilnius, Lithuania
Ilona Kulikiene
Laboratory of Genetic Diagnostic, National Cancer Institute, Santariskiu st. 1, LT-08406 Vilnius, Lithuania
Agne Sestokaite
Laboratory of Genetic Diagnostic, National Cancer Institute, Santariskiu st. 1, LT-08406 Vilnius, Lithuania
Asta Vidrinskaite
Nuclear Medicine Department, National Cancer Institute, Santariskiu st. 1, LT-08660 Vilnius, Lithuania
Arnas Bakavicius
Clinic 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
Feliksas Jankevicius
Clinic 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
Albertas Ulys
Oncourology Department, National Cancer Institute, Santariskiu st. 1, LT-08660 Vilnius, Lithuania
Sonata Jarmalaite
Division of Human Genome Research Centre, Institute of Biosciences, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257 Vilnius, Lithuania
(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.
