OBJECTIVES: 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.

CONCLUSIONS: 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.