Ousati Ashtiani Zahra, Mehrsai Abdol Rasoul, Pourmand Mohammad Reza, Pourmand Gholam Reza
Urology Research Center, Sina Hospital, Tehran University of Medical Sciences, Tehran, 113746911, Iran.
Division of Microbiology, Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, 1417613151, Iran.
Urol J. 2018 Jan 23;15(1):26-31. doi: 10.22037/uj.v0i0.3987.
PIK3CA gene mutations have clinical importance and their presence is associated with therapy response. They are also considered as a molecule for targeted therapy. As regards to their importance, genetic variation within a population as well as among different populations, this study was conducted to detect common mutations of exons 9 and 20 and other probable mutations in PIK3CA gene as well as their frequencies in Iranian bladder cancer patients.
Paired tumor and adjacent normal tissues samples were obtained from 50 bladder cancer patients. Mutations of PIK3CA gene were detected using High Resolution Melting (HRM) analysis which is ahighly sensitive, repeatable, rapid, and cost-effective technique. To determine the precision of the HRM analysis, Sanger sequencing analysis was used.
The result showed that mutations were present in 10% (5/50) of the subjects. The majority of these cases (4/5) had the mutation(s) in exon 9, spanning over five different mutations, among which three of them were actually novel mutations. Further analysis showed that 2 cases had simultaneous mutations for exon 9. In addition to novel mutations, the PIK3CA mutation rate observed in Iranian bladder patients was not as frequent as previous reports and COSMIC.
HRM can be used as a rapid and sensitive method for mutation screening. Dysregulation of PIK3CA gene in bladder cancer reveals its potentials as a mechanistic link for cancer development, which in turn suggests its special use in interventional studies for targeted therapy.
PIK3CA基因突变具有临床重要性，其存在与治疗反应相关。它们也被视为靶向治疗的分子。鉴于其在人群内部以及不同人群之间的重要性，本研究旨在检测PIK3CA基因第9和20外显子的常见突变以及其他可能的突变，及其在伊朗膀胱癌患者中的频率。
从50例膀胱癌患者中获取配对的肿瘤组织和癌旁正常组织样本。使用高分辨率熔解（HRM）分析检测PIK3CA基因的突变，HRM分析是一种高度灵敏、可重复、快速且经济高效的技术。为确定HRM分析的准确性，采用了桑格测序分析。
结果显示，10%（5/50）的受试者存在突变。这些病例中的大多数（4/5）在第9外显子有突变，涵盖五种不同突变，其中三种实际上是新突变。进一步分析表明，2例患者第9外显子同时发生突变。除了新突变外，伊朗膀胱癌患者中观察到的PIK3CA突变率不如先前报道和COSMIC数据库中的频繁。
HRM可作为一种快速且灵敏的突变筛查方法。PIK3CA基因在膀胱癌中的失调揭示了其作为癌症发展机制联系的潜力，这反过来表明其在靶向治疗干预研究中的特殊用途。
