The Mutational and Transcriptional Landscapes of Speckle-Type POZ Protein (SPOP) and Androgen Receptor (AR) in a Single-Center pT3 Prostatectomy Cohort

Abstract

Prostate cancer (PCa) is a heterogeneous disease both clinically and genetically. According to The Cancer Genome Atlas (TCGA), the speckle-type POZ protein (SPOP) mutant form is one of the significant core subtypes of PCa. However, the prognostic value of SPOP variations remains unknown. As a critical PCa driver and an SPOP-targeted protein, androgen receptor (AR) also plays a role in PCa initiation and progression. Thus, we aimed to analyze the mutational status of SPOP and AR with their transcriptional levels in a pathological stage 3 (pT3) prostatectomy cohort consisting of 89 Turkish PCa patients. Targeted sequence analysis and RT-qPCR were performed for SPOP and AR in the benign and malign prostate tissue samples. Our results introduced the two novel pathogenic SPOP variations, C203Y and S236R, in the BTB/POZ domain and a novel pathogenic variant in the ligand-binding domain of AR, R789W. Their predicted pathogenicities and effects on protein features were evaluated by web-based in silico analysis. The overall frequency of SPOP and AR variations for pT3 patients in our population was 3.4% (3/89) and 4.5% (4/89), respectively. The mutational results represented a possible subgroup characterized by carrying the novel variants in SPOP and AR in pT3 PCa patients. In addition to the significant clinicopathological parameters, the mutational results provide a better understanding of the molecular structure of pathologically advanced PCa in the SPOP and AR aspects.