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Analysis of a large prostate cancer family identifies novel and recurrent gene fusion events providing evidence for inherited predisposition


Raspin, K and O'Malley, DE and Marthick, JR and Donovan, S and Malley, RC and Banks, A and Redwig, F and Skala, M and Dickinson, JL and Fitzgerald, LM, Analysis of a large prostate cancer family identifies novel and recurrent gene fusion events providing evidence for inherited predisposition, Prostate, 82, (5) pp. 540-550. ISSN 0270-4137 (2022) [Refereed Article]

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© 2022 Wiley Periodicals

DOI: doi:10.1002/pros.24300


There is strong interest in the characterisation of gene fusions and their use to enhance clinical practices in prostate cancer (PrCa). Significantly, ~50% of prostate tumours harbour a gene fusion. Inherited factors are thought to predispose to these events but, to date, only one study has investigated gene fusions in a familial context. Here, we examined the prevalence and diversity of gene fusions in 14 tumours from a single large PrCa family, PcTas9, using the TruSight® RNA Fusion Panel and Sanger sequencing validation. These fusions were then explored in The Cancer Genome Atlas (TCGA) PrCa data set (n = 494). Overall, 64.3% of PcTas9 tumours harboured a gene fusion, including known erythroblast transformation-specific (ETS) fusions involving ERG and ETV1, and two novel gene fusions, C19orf48:ETV4 and RYBP:FOXP1. Although 3′ ETS genes were overexpressed in PcTas9 and TCGA tumour samples, 3′ fusion of FOXP1 did not appear to alter its expression. In addition, PcTas9 fusion carriers were more likely to have lower-grade disease than noncarriers (p = 0.02). Likewise, TCGA tumours with high-grade disease were less likely to harbour fusions (p = 0.03). Our study further implicates an inherited predisposition to PrCa gene fusion events, which are associated with less aggressive tumours. This knowledge could lead to clinical strategies to predict men at risk for fusion-positive PrCa and, thus, identify patients who are more or less at risk of aggressive disease and/or responsive to particular therapies.

Item Details

Item Type:Refereed Article
Keywords:prostate cancer, gene fusions, genetic predisposition, prostate tumour, TMPRSS2:ERG
Research Division:Biomedical and Clinical Sciences
Research Group:Oncology and carcinogenesis
Research Field:Cancer genetics
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Raspin, K (Dr Kelsie Raspin)
UTAS Author:O'Malley, DE (Miss Dannielle O'Malley)
UTAS Author:Marthick, JR (Mr James Marthick)
UTAS Author:Banks, A (Mrs Annette Banks)
UTAS Author:Dickinson, JL (Professor Joanne Dickinson)
UTAS Author:Fitzgerald, LM (Dr Liesel FitzGerald)
ID Code:148450
Year Published:2022
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-01-11
Last Modified:2022-11-09

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