Abstract 299P
Background
TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare subtype of kidney cancer that predominantly affects young patients. However, the molecular characteristics of TFE3-rRCCs in pediatric and adolescent populations remain poorly understood. This study aimed to comprehensively analyze the genomic and transcriptional profiles of pediatric/adolescent TFE3-rRCCs and compare them with those of adult tumors.
Methods
A total of 17 pediatric/adolescent TFE3-rRCC patients who underwent kidney surgery between 2009 and 2023 were selected from our multicenter TFE3-rRCC database (n = 118). RNA sequencing were conducted from 16 pediatric/adolescent patients and 88 adult patients and Whole-exome sequencing were conducted from 10 pediatric/adolescent patients and 68 adult patients. Detailed clinicopathologic data and patient follow-up information were collected for analysis.
Results
ASPSCR1-TFE3 fusion was the predominant fusion subtype in pediatric/adolescent patients (13/15, 86.7%). In the overall cohort, patients with the ASPSCR1-TFE3 fusion were younger than those with the other fusion subtypes (median age: 21 years vs. 39 years, P <0.001). Pediatric/adolescent TFE3-rRCCs showed similar genomic and transcriptional features to those of adult tumors. Survival analysis demonstrated that disease-free survival and overall survival were comparable between the two groups. Tumors with the same TFE3 fusion subtype shared similar transcriptomic profiles regardless of age. Pediatric/adolescent TFE3-rRCCs with the ASPSCR1-TFE3 fusion displayed an increase in angiogenesis, proliferation and stroma gene signatures and showed a favorable response to anti-PD1 plus TKI combination therapy. In contrast, one patient with a PRCC-TFE3 fusion achieved durable stable disease with mTOR inhibitor-based combination therapies.
Conclusions
This study provides new insights into the genomic and transcriptional features of pediatric/adolescent TFE3-rRCCs, suggesting potential therapeutic strategies tailored for this patient population.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This work was supported by the Natural Science Foundation of China (NSFC 82103097, 82202901, 82203110, 82273047, and 82172785), the China Postdoctoral Science Foundation (2021M692286, 2020M673239 and 2021M692281), the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC21020), and the Natural Science Foundation of Sichuan Province (24NSFSC5394).
Disclosure
All authors have declared no conflicts of interest.