Haoyang Liu , Haolin Liu , Junru Chen , Xiaoxue Yin , Sha Zhu , Xu Hu , Yanfeng Tang , Sike He , Junjie Zhao , Xingming Zhang , Jiayu Liang , Jinge Zhao , Jingjing Guo , Nanshan Yang , Ling Nie , Zhenhua Liu , Ni Chen , Pengfei Shen , Xiaoxi Zeng , Yuntian Chen , Guangxi Sun
{"title":"Molecular Characterization of TFE3-Rearranged Renal Cell Carcinoma in Children and Adolescents","authors":"Haoyang Liu , Haolin Liu , Junru Chen , Xiaoxue Yin , Sha Zhu , Xu Hu , Yanfeng Tang , Sike He , Junjie Zhao , Xingming Zhang , Jiayu Liang , Jinge Zhao , Jingjing Guo , Nanshan Yang , Ling Nie , Zhenhua Liu , Ni Chen , Pengfei Shen , Xiaoxi Zeng , Yuntian Chen , Guangxi Sun","doi":"10.1016/j.modpat.2025.100748","DOIUrl":null,"url":null,"abstract":"<div><div><em>TFE</em>3-rearranged renal cell carcinoma (<em>TFE3</em>-RCC) is a rare but aggressive subtype of kidney cancer that mainly affects young patients. However, the molecular characteristics of <em>TFE3</em>-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 <em>TFE3</em>-RCCs and compare them with those of adult tumors. In this study, 17 pediatric/adolescent patients with <em>TFE3</em>-RCC who underwent kidney surgery between 2009 and 2023 were selected from our multicenter <em>TFE3</em>-RCC database (n = 118). Whole-exome and RNA sequencing were performed on untreated primary tumor tissues. Detailed clinicopathological data and patient follow-up information were collected for analysis. <em>ASPSCR1::TFE3</em> fusion was the most common fusion subtype in pediatric/adolescent patients. Tumors with <em>ASPSCR1::TFE3</em> fusion developed at a younger age compared with those with other fusion subtypes (median age: 21 years vs 39 years, <em>P</em> < .001). Pediatric/adolescent <em>TFE3</em>-RCCs demonstrated similar genomic features and survival outcomes to those in adults. Similar to adult tumors, pediatric/adolescent <em>TFE3</em>-RCCs with <em>ASPSCR1::TFE3</em> 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 <em>TFE3</em>-RCCs, suggesting the importance of transcriptional signatures and the potential therapeutic strategies tailored for this population.</div></div>","PeriodicalId":18706,"journal":{"name":"Modern Pathology","volume":"38 6","pages":"Article 100748"},"PeriodicalIF":5.5000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Modern Pathology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0893395225000444","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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, 17 pediatric/adolescent patients with TFE3-RCC 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 clinicopathological 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 with those with other fusion subtypes (median age: 21 years vs 39 years, P < .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.
期刊介绍：
Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology.
Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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