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Molecular Characterization of TFE3-Rearranged Renal Cell Carcinoma in Children and Adolescents
42 Pages Posted: 30 Sep 2024
More...Abstract
Background: TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare but aggressive subtype of kidney cancer that mainly affects young patients. However, the molecular characteristics of TFE3-rRCCs 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-rRCCs and compare them with those of adult tumors.
Methods: Seventeen pediatric/adolescent TFE3-rRCC patients who underwent kidney surgery between 2009 and 2023 were selected from our multicenter TFE3-rRCC 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.
Findings: 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-rRCCs demonstrated similar genomic features and survival outcomes to those in adults. In both pediatric and adult TFE3-rRCCs, tumors with the same TFE3 fusion subtype exhibited comparable transcriptomic profiles. Similar to adult tumors, pediatric/adolescent TFE3-rRCCs 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.
Interpretation: This study provides comprehensive insights into the genomic and transcriptional features of pediatric/adolescent TFE3-rRCCs, suggesting the importance of fusion identification and the potential therapeutic strategies tailored for this population.
Funding: The Natural Science Foundation of China (NSFC 82472673, 82403766, 82103097, 82202901, 82203110, 82273047, and 82172785), The China Postdoctoral Science Foundation (2024M752231) and The Natural Science Foundation of Sichuan Province (24NSFSC5394 and 2024NSFSC1916).
Declaration of Interest: The authors have declared that no conflict of interest exists.
Ethical Approval: This study was approved by the institutional review board of West China Hospital of Sichuan University, in accordance with the Declaration of Helsinki. All patients or family members provided written consent.
Keywords: TFE3-rRCC, pediatric, genomics, transcription features, clinical outcomes
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