Prevalence of mutations in DNA repair genes in Russian patients with metastatic castration-resistant prostate cancer

Abstract

Background. Prostate cancer is one of the most common malignant tumors in men. Tailored treatment approaches to metastatic castration-resistant prostate cancer based on identification of specific biomarkers have been introduced only recently. So far, the Food and Drug Administration has approved two drugs (olaparib and rucaparib) targeting the DNA repair genes.Aim. To assess the frequency of mutations in the DNA repair genes in the Russian population.Materials and methods. The article uses data from two centers (National Medical Research Radiological Center and A.I. Kryzhanovsky Krasnoyarsk Regional Clinical Oncological Dispensary) which included the largest numbers of patients in the largest Russian multicenter prospective trial ADAM. We performed genotyping of all valid tumor samples from 113 patients with metastatic castration-resistant prostate cancer to identify clinically significant mutations in the DNA repair genes.Results. Next-generation sequencing demonstrated that 27 patients (23.9 %) had clinically significant mutations in DNA repair genes were, including ATM in 6 (5.3 %), BRCA1 in 5 (4.4 %), BRCA2 in 4 (3.5 %), CDK12 in 3 (2.6 %), CHEK2 in 2 (1.8 %), PALB2 in 2 (1.8 %), BRIP1 in 2 (1.8 %), BARD1 in 1 (0.9 %), RAD51B in 1 (0.9 %), and RAD51C in 1 patient (0.9 %).Conclusion. Identification of mutations in the DNA repair genes should become a routine procedure, since a new treatment approach to metastatic castration-resistant prostate cancer is now being introduced.