Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China.
Department of Urology, Southwest Hospital, Army Medical University, Chongqing, PR China.
Urology. 2019 Nov;133:96-102. doi: 10.1016/j.urology.2019.08.016. Epub 2019 Aug 25.
To elucidate the effect of the biallelic somatic TSC2 mutations, identified in one adolescent patient, in renal cell carcinoma (RCC).
Mutation analyses, immunohistochemistry and real-time polymerase chain reaction (PCR) were conducted.
Two novel somatic mutations of TSC2 in unilateral and solitary RCC samples from a 14-year-old female were identified. The pathological features suggest the tumor as a clear-cell renal cell carcinoma. In addition, immunohistochemistry revealed elevated levels of phosphorylated S6K1. Results from in vitro cellular experiments suggest that the mutant TSC2 proteins were quickly degraded and they failed to repress the phosphorylation of S6K1 and STAT3, which leads to constitutive activation of mTORC1 pathway and ultimately cause the development of RCC.
Detecting TSC2 mutation in patients with early RCC onset would be beneficial and mTOR inhibitor could be a therapeutic option for TSC2 mutation-induced RCC.
阐明在一名青少年患者中发现的 TSC2 双等位体细胞突变对肾细胞癌（RCC）的影响。
进行突变分析、免疫组织化学和实时聚合酶链反应（PCR）。
在一名 14 岁女性单侧和单发 RCC 样本中发现了 TSC2 的两个新的体细胞突变。病理特征提示该肿瘤为透明细胞肾细胞癌。此外，免疫组织化学显示磷酸化 S6K1 的水平升高。体外细胞实验结果表明，突变的 TSC2 蛋白迅速降解，无法抑制 S6K1 和 STAT3 的磷酸化，导致 mTORC1 通路的持续激活，最终导致 RCC 的发生。
在早期 RCC 发病的患者中检测 TSC2 突变将是有益的，mTOR 抑制剂可能是 TSC2 突变诱导的 RCC 的治疗选择。
