Analysis of Homologous Recombination Deficiency in Prostate Cancer

Background. Mutations in homologous recombination repair (HRR) genes (BRCA2, ATM, CHEK2, NBN, etc.) are found in 20-25 % of patients with metastatic prostate cancer (PC) and are an indication for prescription of PARP inhibitors. Sensitivity to these drugs results from homologous recombination deficiency (HRD) in the tumor. It is currently not fully elucidated which HRR genes besides BRCA1/2 cause HRD. The aim of the study was to evaluate the presence of homologous recombination deficiency in PC associated with mutations in different HRR genes. Material and Methods. Paired tumor and normal DNA samples from 272 PC patients were examined using the HiSNP Ultra Panel v1.0 NGS panel (Nanodigmbio). Tumor copy number variation profiles were used to obtain the HRD score, which was determined as the unweighted sum of three characteristics: the number of chromosomal regions with loss of heterozygosity (LOH), large scale state transitions (LST), and telomeric allelic imbalances (TAI). HRD scores in different PC categories were compared using the Mann-Whitney test.