Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 211-63, Jordan.
Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid 211-63, Jordan.
Asian Pac J Cancer Prev. 2020 Nov 1;21(11):3365-3371. doi: 10.31557/APJCP.2020.21.11.3365.
Recent advances in molecular biology make the identification of prostate cancer (PC) subsets a priority for more understanding of the molecular pathogenesis and treatment options. Genetic alterations in many genes such as TP53, SPOP and PIK3CA genes have been reported in PC with variable frequencies worldwide. We aimed to investigate genetic alterations in the hotspot lesions of TP53, SPOP and PIK3CA genes by direct sequencing and the expression of TP53 and PIK3CA by RT-PCR in prostate cancer, and to explore the correlation between TP53, SPOP and PIK3CA alterations and tumorigenesis of prostate cancer. Seventy-nine FFPE prostate samples from patients who underwent radical prostatectomy were obtained, subjected to genomic DNA extraction and sequenced for mutations in exons 5, 6, 7 and 8 of TP53 gene, exons 4 and 5 of SPOP gene and exons 9 and 20 of PIK3CA gene. RT-PCR was performed for the expression evaluation of the PIK3CA gene. Our results showed a high frequency of TP53 mutations (11/79, 13.9 %) in the selected population. On the other hand, SPOP and PIK3CA genes did not show any genetic alteration in the sequenced exons. PIK3CA gene overexpression was detected in 6% of the cohort by RT-PCR. TP53 mutation is the most frequent genetic alteration and likely has a major role in the pathogenesis of PC in the Jordanian population.
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近年来,分子生物学的进展使得鉴定前列腺癌 (PC) 亚群成为优先事项,以便更深入地了解分子发病机制和治疗选择。TP53、SPOP 和 PIK3CA 等许多基因的遗传改变已在全球范围内报道存在于 PC 中,其频率各不相同。我们旨在通过直接测序研究 TP53、SPOP 和 PIK3CA 基因热点病变中的遗传改变,以及通过 RT-PCR 研究 TP53 和 PIK3CA 基因在前列腺癌中的表达,并探讨 TP53、SPOP 和 PIK3CA 改变与前列腺癌发生之间的相关性。我们从接受根治性前列腺切除术的患者中获得了 79 个 FFPE 前列腺样本,对这些样本进行了基因组 DNA 提取,并对 TP53 基因的外显子 5、6、7 和 8、SPOP 基因的外显子 4 和 5 以及 PIK3CA 基因的外显子 9 和 20 进行了测序,以检测突变。进行 RT-PCR 以评估 PIK3CA 基因的表达。我们的结果显示,在所选择的人群中,TP53 突变的频率很高 (11/79, 13.9%)。另一方面,SPOP 和 PIK3CA 基因在测序的外显子中没有显示任何遗传改变。通过 RT-PCR 检测到 6%的队列中存在 PIK3CA 基因过表达。TP53 突变是最常见的遗传改变,可能在约旦人群的 PC 发病机制中起主要作用。