Title Urinary DNA as a tool for germline and somatic mutation detection in castration-resistant prostate cancer patients /
Authors Januškevičius, Tomas ; Sabaliauskaitė, Rasa ; Dabkevičienė, Daiva ; Vaicekauskaitė, Ieva ; Kulikienė, Ilona ; Šeštokaitė, Agnė ; Vidrinskaitė, Asta ; Bakavičius, Arnas ; Jankevičius, Feliksas ; Ulys, Albertas ; Jarmalaitė, Sonata
DOI 10.3390/biomedicines11030761
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Is Part of Biomedicines.. Basel : MDPI. 2023, vol. 11, iss. 3, art. no. 761, p. 394-424.. eISSN 2227-9059
Keywords [eng] DNA damage repair ; BRCA1 ; BRCA2 genes ; castration-resistant prostate cancer ; abiraterone acetate
Abstract [eng] 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.
Published Basel : MDPI
Type Journal article
Language English
Publication date 2023
CC license CC license description