Germline DNA Damage Response Gene Mutations in Localized Prostate Cancer
<i>Background and Objectives</i>: 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’...
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/60/1/73 |
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| author | Tomas Januskevicius Ieva Vaicekauskaite Rasa Sabaliauskaite Augustinas Matulevicius Alvydas Vezelis Albertas Ulys Sonata Jarmalaite Feliksas Jankevicius |
| author_facet | Tomas Januskevicius Ieva Vaicekauskaite Rasa Sabaliauskaite Augustinas Matulevicius Alvydas Vezelis Albertas Ulys Sonata Jarmalaite Feliksas Jankevicius |
| author_sort | Tomas Januskevicius |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: 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. <i>Materials and Methods</i>: Germline DDR gene mutations were assessed prospectively in DNA samples from 139 patients, using a five-gene panel (<i>BRCA1</i>, <i>BRCA2</i>, <i>ATM</i>, <i>CHEK2</i>, and <i>NBN</i>) targeted next-generation sequencing. <i>Results</i>: 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, <i>p</i> = 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. <i>BRCA1</i>/<i>BRCA2</i>/<i>ATM</i> mutation carriers were 2.6 times more likely to have a higher (>1) cISUP grade group compared to those with a <i>CHEK2</i> mutation (<i>p</i> = 0.27). However, the number of cISUP > 1-grade patients with a <i>CHEK2</i> mutation was significantly higher in advanced PCa than in localized PCa: 66.67% vs. 23.08% (<i>p</i> = 0.047). <i>Conclusions</i>: 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. |
| first_indexed | 2024-03-08T10:41:00Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-08T10:41:00Z |
| publishDate | 2023-12-01 |
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| spelling | doaj.art-15eedc653a364530a95de81e507b979c2024-01-26T17:35:14ZengMDPI AGMedicina1010-660X1648-91442023-12-016017310.3390/medicina60010073Germline DNA Damage Response Gene Mutations in Localized Prostate CancerTomas Januskevicius0Ieva Vaicekauskaite1Rasa Sabaliauskaite2Augustinas Matulevicius3Alvydas Vezelis4Albertas Ulys5Sonata Jarmalaite6Feliksas Jankevicius7Clinic of Gastroenterology, Nephro-Urology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, M. K. Ciurlionio St. 21/27, LT-03101 Vilnius, LithuaniaLaboratory of Genetic Diagnostic, National Cancer Institute, Santariskiu St. 1, LT-08406 Vilnius, LithuaniaLaboratory of Genetic Diagnostic, National Cancer Institute, Santariskiu St. 1, LT-08406 Vilnius, LithuaniaDivision of Human Genome Research Centre, Institute of Biomedical Sciences, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257 Vilnius, LithuaniaOncourology Department, National Cancer Institute, Santariskiu St. 1, LT-08660 Vilnius, LithuaniaOncourology Department, National Cancer Institute, Santariskiu St. 1, LT-08660 Vilnius, LithuaniaLaboratory of Genetic Diagnostic, National Cancer Institute, Santariskiu St. 1, LT-08406 Vilnius, LithuaniaClinic 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<i>Background and Objectives</i>: 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. <i>Materials and Methods</i>: Germline DDR gene mutations were assessed prospectively in DNA samples from 139 patients, using a five-gene panel (<i>BRCA1</i>, <i>BRCA2</i>, <i>ATM</i>, <i>CHEK2</i>, and <i>NBN</i>) targeted next-generation sequencing. <i>Results</i>: 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, <i>p</i> = 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. <i>BRCA1</i>/<i>BRCA2</i>/<i>ATM</i> mutation carriers were 2.6 times more likely to have a higher (>1) cISUP grade group compared to those with a <i>CHEK2</i> mutation (<i>p</i> = 0.27). However, the number of cISUP > 1-grade patients with a <i>CHEK2</i> mutation was significantly higher in advanced PCa than in localized PCa: 66.67% vs. 23.08% (<i>p</i> = 0.047). <i>Conclusions</i>: 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.https://www.mdpi.com/1648-9144/60/1/73DNA damage responsegermline mutationlocalized prostate cancernext-generation sequencing |
| spellingShingle | Tomas Januskevicius Ieva Vaicekauskaite Rasa Sabaliauskaite Augustinas Matulevicius Alvydas Vezelis Albertas Ulys Sonata Jarmalaite Feliksas Jankevicius Germline DNA Damage Response Gene Mutations in Localized Prostate Cancer Medicina DNA damage response germline mutation localized prostate cancer next-generation sequencing |
| title | Germline DNA Damage Response Gene Mutations in Localized Prostate Cancer |
| title_full | Germline DNA Damage Response Gene Mutations in Localized Prostate Cancer |
| title_fullStr | Germline DNA Damage Response Gene Mutations in Localized Prostate Cancer |
| title_full_unstemmed | Germline DNA Damage Response Gene Mutations in Localized Prostate Cancer |
| title_short | Germline DNA Damage Response Gene Mutations in Localized Prostate Cancer |
| title_sort | germline dna damage response gene mutations in localized prostate cancer |
| topic | DNA damage response germline mutation localized prostate cancer next-generation sequencing |
| url | https://www.mdpi.com/1648-9144/60/1/73 |
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