Precision medicine targets for prostate cancers in African American men

Abstract

To investigate molecular mechanisms underlying prostate cancer health disparities, the primary prostate epithelial cell cultures were established from the tumors and adjacent non-tumor tissues of prostatectomy specimens of African American (AA) men surgically treated for cancer. We performed whole genome sequencing of 10 tumor samples paired with 10 non-tumor controls derived from the same donors using next generation sequencing technologies. Here, we report that tumor cells harbor various mutations with insertion/deletion variants, some of which are unique in individual specimens. Comparative analyses of genomic profiling revealed that 40% of the cohort harbored more than 20 mutated genes with high impactful consequences, coinciding with clinical-pathological characteristics of patients, including higher Gleason’s grade and T3 clinical stage. Several mutated genes were oncogenes or potentially oncogenic variants of tumor suppressors, affecting key pathways in the carcinogenic process. Our study highlights unique somatic gene alterations in AA patient-derived prostate tumor cells offering potentially targetable drivers in support of precision medicine for individual prostate cancers rather than disease specific therapies.