Germline variant screening with targeted next generation sequencing in prostate cancer: phenotype-genotype correlation

Background/aim: Next generation sequencing provides new information about the molecular pathogenesis of cancer. We used a targeted NGS-based multiple gene panel comprising prostate cancer (PCa) predisposing genes to assess the prevalence of germline mutations in PCa patients. Material and methods: In a cohort of twenty-one PCa patients with a family history of cancer, a targeted multigene panel consisting of 39 genes associated with hereditary cancer was created and analyzed using the next generation sequencing method. The novel and pathogenic mutations detected were confirmed by Sanger sequencing method. Thereafter, the data obtained were evaluated using different genomic variant classifiers and databases. Results: With an incidence of less than 5% in different populations (MAF<0.05); a total of 81 variants were identified, including 41 missense, 16 synonymous, 3 splice-site, 11 intronic, 5 in-del and 5 novels. According to the ACMG criteria, 5 (6.2%) of these variants are pathogenic/likely pathogenic; 5 (6.2%) of them were classified as novel variants. In addition, variants having very low-frequency and unknown clinical significance (VUS) in the databases were detected. Conclusion: The findings we obtained from this study contributed to the understanding the genetic pathogenesis of PCa, determining the frequency of mutations in the population, and revealing the genotype-phenotype correlations. Additionally, we demonstrated that using multigene panel-based genetic tests rather than single-gene tests in germline mutation screening in hereditary PCa will be more beneficial in terms of genetic counseling.

Automated summary

The study aimed to assess the prevalence of germline mutations in prostate cancer patients using a targeted NGS-based multiple gene panel. The results showed a low incidence of pathogenic/likely pathogenic variants and identified novel variants. The findings contribute to understanding the genetic pathogenesis of prostate cancer and highlight the benefits of using multigene panel-based genetic tests for genetic counseling.