Transcriptomic profiling and genomic rearrangement landscape of Nigerian prostate cancer. Issue 5 (4th January 2023) - Mavura, Yusuph
Abstract: Background: Men of African ancestry have disproportionately high incidence rates of prostate cancer (PCa) and have high mortality rates. While there is evidence for a higher genetic predisposition for incidence of PCa in men of African ancestry compared to men of European ancestry, there have been few transcriptomic studies on PCa in men of African ancestry in the African continent. Objective: We performed transcriptomic profiling and fusion analysis on bulk RNA sequencing (RNA‐seq) samples from 24 Nigerian PCa patients to investigate the transcriptomic and genomic rearrangement landscape of PCa in Nigerian men. Design: Bulk RNA‐seq was performed on 24 formalin‐fixed paraffin‐embeded (FFPE) prostatectomy specimens of Nigerian men. Transcriptomic analysis was performed on 11 high‐quality samples. Arriba Fusion and STAR Fusion were used for fusion detection. Results: 4/11 (36%) of the samples harbored an erythroblast transformation‐specific (ETS) fusion event; 1/11 (9%) had a TMPRSS2‐ERG fusion; 2/11 had a TMPRSS2‐ETV5 fusion, and 1/11 had a SLC45A3‐SKIL fusion. Hierarchical clustering of normalized and mean‐centered gene expression showed clustering of fusion positive samples. Furthermore, we developed gene set signatures for Nigerian PCa based on fusion events. By projecting the cancer genome atlas prostate adenocarcinoma (TCGA‐PRAD) bulk RNA‐seq data set onto the transcriptional space defined by these signatures derived from Nigerian PCa patients, we identified a positive correlation between the Nigerian fusion signature and fusion positive samples in the TCGA‐PRAD data set. Conclusions: Less frequent ETS fusion events other than TMPRSS2‐ERG such as TMPRSS2‐ETV5 and non‐ETS fusion events such as SLC45A3‐SKIL may be more common in PCa in Nigerian men. This study provides useful working transcriptomic signatures that characterize oncogenic states representative of specific gene fusion events in PCa from Nigerian men. Patient Summary: Using RNA‐Seq data, we conducted a transcriptomic analysis on FFPE PCa samples from 11 men of Nigerian descent. We found that less frequent fusion events other than TMPRSS2‐ERG such as TMPRSS2‐ETV5, SLC45A3‐SKIL may be more common in PCa in Nigerian men.