BRCA-deficient metastatic prostate cancer has an adverse prognosis and distinct genomic phenotypeResearch in context

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:
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