Autor: |
Heidi Fettke, Chao Dai, Edmond M. Kwan, Tiantian Zheng, Pan Du, Nicole Ng, Patricia Bukczynska, Maria Docanto, Louise Kostos, Siavash Foroughi, Stephen Brown, Lisa-Jane K. Graham, Kate Mahon, Lisa G. Horvath, Shidong Jia, Manish Kohli, Arun A. Azad |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
EBioMedicine, Vol 95, Iss , Pp 104738- (2023) |
Druh dokumentu: |
article |
ISSN: |
2352-3964 |
DOI: |
10.1016/j.ebiom.2023.104738 |
Popis: |
Summary: Background: Genomic alterations in DNA damage response (DDR) genes are common in metastatic castration-resistant prostate cancer (mCRPC). Understanding how these genomic events impact prognosis and/or treatment response is vital for optimising clinical outcomes. Methods: Targeted sequencing was performed on 407 plasma samples from 375 men with mCRPC. Using the CLIA-certified PredicineCARE™ cell-free DNA (cfDNA) assay, pathogenic alterations in 152 key genes (including 27 DDR-related genes) were assessed, as was the presence and mechanisms of biallelic loss in BRCA2. Findings: At least one DDR alteration was present in 34.5% (129/375) of patients (including monoallelic alterations). The most frequently altered DDR genes were BRCA2 (19%), ATM (13%), FANCA (5%), CHEK2 (5%) and BRCA1 (3%). Patients with BRCA alterations, especially BRCA2, had significantly worse progression-free survival (PFS) (Hazard ratio (HR) 3.3 [95% CI 1.9–6.0]; Cox regression p |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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