Fusion Genes in Prostate Cancer: A Comparison in Men of African and European Descent

Abstract

Prostate cancer is one of the most prevalent cancers worldwide, particularly affecting men living a western lifestyle and of African descent, suggesting risk factors that are genetic, environmental, and socioeconomic in nature. In the USA, African American (AA) men are disproportionately affected, on average suffering from a higher grade of the disease and at a younger age compared to men of European descent (EA). Fusion genes are chimeric products formed by the merging of two separate genes occurring as a result of chromosomal structural changes, for example, inversion or trans/cis-splicing of neighboring genes. They are known drivers of cancer and have been identified in 20% of cancers. Improvements in genomics technologies such as RNA-sequencing coupled with better algorithms for prediction of fusion genes has added to our knowledge of specific gene fusions in cancers. At present AA are underrepresented in genomic studies of prostate cancer. The primary goal of this study was to examine molecular differences in predicted fusion genes in a cohort of AA and EA men in the context of prostate cancer using computational approaches. RNA was purified from prostate tissue specimens obtained at surgery from subjects enrolled in the study. Fusion gene predictions were performed using four different fusion gene detection programs. This identified novel putative gene fusions unique to AA and suggested that the fusion gene burden was higher in AA compared to EA men.