| Autor: |
Januskevicius T; 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., Vaicekauskaite I; Laboratory of Genetic Diagnostic, National Cancer Institute, Santariskiu St. 1, LT-08406 Vilnius, Lithuania.; Division of Human Genome Research Centre, Institute of Biomedical Sciences, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257 Vilnius, Lithuania., Sabaliauskaite R; Laboratory of Genetic Diagnostic, National Cancer Institute, Santariskiu St. 1, LT-08406 Vilnius, Lithuania.; Division of Human Genome Research Centre, Institute of Biomedical Sciences, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257 Vilnius, Lithuania., Matulevicius A; Division of Human Genome Research Centre, Institute of Biomedical Sciences, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257 Vilnius, Lithuania.; Urology Centre, Vilnius University Hospital Santaros Klinikos, Santariskiu St. 2, LT-08661 Vilnius, Lithuania., Vezelis A; Oncourology Department, National Cancer Institute, Santariskiu St. 1, LT-08660 Vilnius, Lithuania., Ulys A; Oncourology Department, National Cancer Institute, Santariskiu St. 1, LT-08660 Vilnius, Lithuania., Jarmalaite S; Laboratory of Genetic Diagnostic, National Cancer Institute, Santariskiu St. 1, LT-08406 Vilnius, Lithuania.; Division of Human Genome Research Centre, Institute of Biomedical Sciences, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257 Vilnius, Lithuania., Jankevicius F; 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.; Urology Centre, Vilnius University Hospital Santaros Klinikos, Santariskiu St. 2, LT-08661 Vilnius, Lithuania. |
| Abstrakt: |
Background and Objectives : Germline DNA damage response (DDR) gene mutations correlate with increased prostate cancer (PCa) risk and a more aggressive form of the disease. DDR mutation testing is recommended for metastatic PCa cases, while eligible information about the mutations' burden in the early-stage localized PCa is still limited. This study is aimed at the prospective detection of DDR pathway mutations in cases with localized PCa and correlation with clinical, histopathological, and radiological data. A comparison to the previously assessed cohort of the advanced PCa was performed. Materials and Methods : Germline DDR gene mutations were assessed prospectively in DNA samples from 139 patients, using a five-gene panel ( BRCA1 , BRCA2 , ATM , CHEK2 , and NBN ) targeted next-generation sequencing. Results : This study revealed an almost three-fold higher risk of localized PCa among mutation carriers as compared to non-carriers (OR 2.84 and 95% CI: 0.75-20.23, p = 0.16). The prevalence of germline DDR gene mutations in PCa cases was 16.8% (18/107) and they were detected only in cases with PI-RADS 4/5 lesions. BRCA1 / BRCA2 / ATM mutation carriers were 2.6 times more likely to have a higher (>1) cISUP grade group compared to those with a CHEK2 mutation ( p = 0.27). However, the number of cISUP > 1-grade patients with a CHEK2 mutation was significantly higher in advanced PCa than in localized PCa: 66.67% vs. 23.08% ( p = 0.047). Conclusions : The results of our study suggest the potential of genetic screening for selected DDR gene mutations for early identification of cases at risk of aggressive PCa. |
