Transcriptomic profiling and genomic rearrangement landscape of Nigerian prostate cancer

Author:

Mavura Yusuph12ORCID,Song Hanbing234,Xie Jamie234,Tamayo Pablo567,Mohammed Abdullahi8,Lawal Ahmad T.9,Bello Ahmad9,Ibrahim Sani10,Faruk Mohammed8,Huang Franklin W.23411

Affiliation:

1. Department of Epidemiology and Biostatistics University of California San Francisco California USA

2. Institute for Human Genetics University of California San Francisco California USA

3. Department of Medicine, Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center University of California San Francisco California USA

4. Bakar Computational Health Sciences Institute University of California San Francisco California USA

5. Moores Cancer Center University of California San Diego La Jolla California USA

6. Center for Novel Therapeutics University of California San Diego La Jolla California USA

7. Department of Medicine University of California San Diego La Jolla California USA

8. Department of Pathology, Faculty of Basic Clinical Sciences, College of Medical Sciences Ahmadu Bello University Zaria Nigeria

9. Department of Surgery, Division of Urology, Faculty of Clinical Sciences, College of Medical Sciences Ahmadu Bello University Zaria Nigeria

10. Department of Biochemistry, Faculty of Life Sciences Ahmadu Bello University Zaria Nigeria

11. San Francisco Veterans Affairs Health Care System San Francisco California USA

Abstract

AbstractBackgroundMen 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.ObjectiveWe 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.DesignBulk 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.Results4/11 (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.ConclusionsLess 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.

Publisher

Wiley

Subject

Urology,Oncology

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