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Review
. 2025 May 20:2025:4084224.
doi: 10.1155/sci5/4084224. eCollection 2025.

Updates on SPOP Gene Mutations in Prostate Cancer and Computational Insights From TCGA cBioPortal Database

Suleiman Zakari  1   2   3 , Solomon O Rotimi  1   2 , Chandra Tatsha Bholah  4 , Olubanke O Ogunlana  1   2
Affiliations
Review

Updates on SPOP Gene Mutations in Prostate Cancer and Computational Insights From TCGA cBioPortal Database

Suleiman Zakari et al. Scientifica (Cairo). .

Abstract

Speckle-type pox virus and zinc finger protein (SPOP) has emerged as a key focus in prostate cancer research due to its critical role in regulating the androgen receptor (AR) signaling pathway. This review aims to comprehensively summarize current knowledge on SPOP gene mutations in prostate cancer, emphasizing their importance in disease characterization and identification of therapeutic targets. A systematic literature search was conducted across multiple databases, including PubMed, Web of Science, Scopus, and Google Scholar. In addition, this study uses computational approaches and data from the TCGA cBioPortal database to explore the landscape of SPOP mutations in prostate cancer. After screening 682 articles and following systematic selection steps, 56 high-quality articles were included. Computational analysis of TCGA cBioPortal data revealed a SPOP mutation prevalence of 5%-6%, along with significant alterations in AR signaling and epigenetic regulation. SPOP mutations disrupt substrate recognition, leading to dysregulation of downstream pathways such as AR signaling and chromatin remodeling. Notably, SPOP-mutant prostate cancers are mutually exclusive with TMPRSS2-ERG fusions and enriched for Wnt pathway alterations. Patients with SPOP mutations demonstrate prolonged responses to androgen deprivation therapy (ADT), although concurrent mutations in TP53 or DNA repair genes negatively impact outcomes. While their prognostic significance continues to evolve, their impact on the AR pathway highlights their potential as therapeutic targets. The clinical implications of SPOP mutations are substantial, as they are linked to variations in treatment response and disease progression, thus serving as valuable biomarkers for risk stratification and prognosis.

Keywords: SPOP gene; SPOP mutations; TCGA cBioPortal; androgen receptor; prostate cancer; therapeutic targets.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Study flowchart showing search output.
Figure 2
Figure 2
Structure of SPOP protein.
Figure 3
Figure 3
SPOP mutations across different cancer types from the cBioPortal database (https://www.cbioportal.org/).
Figure 4
Figure 4
Type of mutation based on mRNA expression from the cBioPortal database (https://www.cbioportal.org/).
Figure 5
Figure 5
Combine study of SPOP mutation gene from the cBioPortal database (https://www.cbioportal.org/).
See this image and copyright information in PMC

References

    1. CDC. Prostate Cancer . 2023. What is Prostate Cancer? https://www.cdc.gov/cancer/prostate/basic_info/what-is-prostate-cancer.htm .
    1. He Y., Hooker E., Yu E.-J., Wu H., Cunha G. R., Sun Z. An Indispensable Role of Androgen Receptor in Wnt Responsive Cells During Prostate Development, Maturation, and Regeneration. Stem Cells (Dayton) . 2018;36(6):891–902. doi: 10.1002/stem.2806. - DOI - PMC - PubMed
    1. Yang X., Zhu Q. SPOP in Cancer: Phenomena, Mechanisms and Its Role in Therapeutic Implications. Genes . 2022;13(11):p. 2051. doi: 10.3390/genes13112051. - DOI - PMC - PubMed
    1. Al Zoubi M., Otoum R., Alorjani M., et al. TP53, SPOP and PIK3CA Genes Status in Prostate Cancer. Asian Pacific Journal of Cancer Prevention . 2020;21(11):3365–3371. doi: 10.31557/APJCP.2020.21.11.3365. - DOI - PMC - PubMed
    1. Barbieri C. E., Baca S. C., Lawrence M. S., et al. Exome Sequencing Identifies Recurrent SPOP, FOXA1 and MED12 Mutations in Prostate Cancer. Nature Genetics . 2012;44(6):685–689. doi: 10.1038/ng.2279. - DOI - PMC - PubMed

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