Identification and characterization of novel fusion genes in prostate cancer by targeted RNA capture and next-generation sequencing

Gene fusions play critical roles in the development and progression of prostate cancer, and have been used as molecular biomarkers for diagnosis of the malignant disease. To further explore the novel fusions in prostate cancer, we performed targeted RNA capture and next-generation sequencing in a cohort of 52 prostate cancer patients, identified and validated 14 fusion events (7 types of fusion genes) in 12 cases, including three novel fusion genes. We characterized a chromosome rearrangement-induced trigenic KLK2-DGKB-ETV1 fusion, which may function as a non-coding RNA to upregulate the expression of the wild-type ETV1 protein in the tumor tissue. Additionally, we detected two novel fusion forms of HNRNPA2B1-ETV1 and SLC45A2-AMACR fusions, respectively. Interestingly, fusion events participated by kinase genes, which frequently occurred in other human cancers, were not present in these prostate cancer cases, suggesting discrepant gene fusion patterns in different cancers. These findings expand the genetic spectrum of prostate cancer and provide insight into diagnosis of this prevalent disease.