Jian Pang1, Linang Wang1, Jing Xu1, Qiubo Xie1, Qiuli Liu1, Dali Tong1, Gaolei Liu1, Yiqiang Huang1, Xingxia Yang1, Jinhong Pan2, Xiaochu Yan3, Qiang Ma4, Dianzheng Zhang5, Jun Jiang6. 1. Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China. 2. Department of Urology, Southwest Hospital, Army Medical University, Chongqing, PR China. 3. Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University, Chongqing, PR China. 4. Department of Pathology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China. 5. Department of Biomedical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, PA. 6. Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, PR China. Electronic address: jiangjun_64@163.com.
Abstract
OBJECTIVE: To elucidate the effect of the biallelic somatic TSC2 mutations, identified in one adolescent patient, in renal cell carcinoma (RCC). METHODS: Mutation analyses, immunohistochemistry and real-time polymerase chain reaction (PCR) were conducted. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: To elucidate the effect of the biallelic somatic TSC2 mutations, identified in one adolescent patient, in renal cell carcinoma (RCC). METHODS: Mutation analyses, immunohistochemistry and real-time polymerase chain reaction (PCR) were conducted. RESULTS: 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. CONCLUSION: 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.
Authors: Kristyna Prochazkova; Nikola Ptakova; Reza Alaghehbandan; Sean R Williamson; Tomáš Vaněček; Josef Vodicka; Vladislav Treska; Joanna Rogala; Kristyna Pivovarcikova; Kvetoslava Michalova; Maryna Slisarenko; Milan Hora; Michal Michal; Ondrej Hes Journal: Cancers (Basel) Date: 2021-11-24 Impact factor: 6.639