Molecular characterization of TFE3-rearranged renal cell carcinoma in children and adolescents.

TFE3-rearranged renal cell carcinoma (TFE3-RCC) is a rare but aggressive subtype of kidney cancer that mainly affects young patients. However, the molecular characteristics of TFE3-RCCs in children and adolescents remain poorly understood. To this end, we performed a comprehensive study to characterize the genomic and transcriptional profiles of pediatric/adolescent TFE3-RCCs and compare them with those of adult tumors. In this study, seventeen pediatric/adolescent TFE3-RCC patients who underwent kidney surgery between 2009 and 2023 were selected from our multicenter TFE3-RCC database (n = 118). Whole-exome and RNA sequencing were performed on untreated primary tumor tissues. Detailed clinicopathologic data and patient follow-up information were collected for analysis. ASPSCR1::TFE3 fusion was the most common fusion subtype in pediatric/adolescent patients. Tumors with ASPSCR1::TFE3 fusion developed at a younger age compared to those with other fusion subtypes (median age: 21 years vs. 39 years, P <0.001). Pediatric/adolescent TFE3-RCCs demonstrated similar genomic features and survival outcomes to those in adults. Similar to adult tumors, pediatric/adolescent TFE3-RCCs with ASPSCR1::TFE3 fusion displayed higher expression of angiogenesis, proliferation, and stroma gene signatures and responded favorably to anti-PD1 plus tyrosine kinase inhibitor combination therapy. This study provides comprehensive insights into the genomic and transcriptional features of pediatric/adolescent TFE3-RCCs, suggesting the importance of transcriptional signatures and the potential therapeutic strategies tailored for this population.