Targeted sequencing reveals germline DNA damage repair variants impact disease aggression in metastatic prostate cancer patients, indicating genetic testing importance.
Key Points
The study aims to explore the landscape of inherited DNA damage repair gene variants and their clinical relevance in metastatic prostate cancer patients.
Performed targeted sequencing on peripheral blood DNA of 3005 metastatic prostate cancer patients.
Searched for small variants and large structural variants across 32 DDR-associated genes.
Included only pathogenic variants or those predicted to truncate the protein.
Conducted correlative analysis with clinical data available for 81% of the patients.
Performed selective tumor DNA sequencing to determine somatic DDR gene status.
Detected germline DDR gene variants in 269 patients (9% of cohort).
Most common variants were in BRCA2 (2.8%), ATM (1.2%), and CHEK2 (1.1%).
Second allele inactivation observed in 93% of BRCA2 and 100% of ATM variants.
Patients with BRCA2 variants had worse outcomes, including increased disease grade and decreased overall survival.
Identified novel gene-truncating structural variants in 11 patients.