Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr;82(5):540-550.
doi: 10.1002/pros.24300. Epub 2022 Jan 7.

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

Affiliations

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

Kelsie Raspin et al. Prostate. 2022 Apr.

Abstract

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.

Keywords: TMPRSS2:ERG; familial prostate cancer; gene fusions; genetic predisposition; prostate tumour.

PubMed Disclaimer

References

REFERENCES

    1. Petrovics G, Liu A, Shaheduzzaman S, et al. Frequent overexpression of ETS-related gene-1 (ERG1) in prostate cancer transcriptome. Oncogene. 2005;24:3847-3852.
    1. Tomlins SA, Rhodes DR, Perner S, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310:644-648.
    1. Kohaar I, Li Q, Chen Y, et al. Association of germline genetic variants with TMPRSS2-ERG fusion status in prostate cancer. Oncotarget. 2020;11:1321-1333.
    1. Kong DP, Chen R, Zhang CL, et al. Prevalence and clinical application of TMPRSS2-ERG fusion in Asian prostate cancer patients: a large-sample study in Chinese people and a systematic review. Asian J Androl. 2020;22:200-207.
    1. Xiao Q, Sun Y, Dobi A, et al. Systematic analysis reveals molecular characteristics of ERG-negative prostate cancer. Sci Rep. 2018;8:12868.

Publication types

MeSH terms

LinkOut - more resources