Bursa Uludag University, Faculty of Medicine, Medical Biology Department, Gorukle, Bursa, Turkey.
Bursa Uludag University, Faculty of Medicine, Medical Pathology Department, Gorukle, Bursa, Turkey.
J Environ Pathol Toxicol Oncol. 2024;43(1):15-29. doi: 10.1615/JEnvironPatholToxicolOncol.2023048095.
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.
前列腺癌 (PCa) 在临床和遗传上均具有异质性。根据癌症基因组图谱 (TCGA)，斑点型 POZ 蛋白 (SPOP) 突变形式是 PCa 的重要核心亚型之一。然而，SPOP 变异的预后价值尚不清楚。作为关键的 PCa 驱动因子和 SPOP 靶向蛋白，雄激素受体 (AR) 也在 PCa 的发生和进展中发挥作用。因此，我们旨在分析由 89 名土耳其 PCa 患者组成的病理分期 3 (pT3) 前列腺切除术队列中 SPOP 和 AR 的突变状态及其转录水平。对良性和恶性前列腺组织样本中的 SPOP 和 AR 进行靶向序列分析和 RT-qPCR。我们的结果在 BTB/POZ 结构域中引入了两个新的致病性 SPOP 变异，C203Y 和 S236R，以及 AR 配体结合域中的一个新的致病性变异 R789W。通过基于网络的计算机分析评估了它们的预测致病性及其对蛋白质特征的影响。在我们的人群中，pT3 患者的 SPOP 和 AR 变异的总频率分别为 3.4% (3/89) 和 4.5% (4/89)。突变结果代表了 pT3 PCa 患者中携带 SPOP 和 AR 新变异的可能亚组。除了显著的临床病理参数外，突变结果还从 SPOP 和 AR 方面提供了对病理性晚期 PCa 的分子结构的更好理解。
