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Updated: Oct 21, 2025
Targeted RNA Sequencing Assay to Characterize Gene Expression and Genomic Alterations
Published on: August 4, 2016
Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma
Guangxi Sun1, Junru Chen1, Jiayu Liang1
1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare and heterogeneous subtype of kidney cancer with no standard treatment for advanced disease. We describe comprehensive molecular characteristics of 63 untreated primary TFE3-tRCCs based on whole-exome and RNA sequencing. TFE3-tRCC is highly heterogeneous, both clinicopathologically and genotypically. ASPSCR1-TFE3 fusion and several somatic copy number alterations, including the loss of 22q, are associated with aggressive features and poor outcomes. Apart from tumors with MED15-TFE3 fusion, most TFE3-tRCCs exhibit low PD-L1 expression and low T-cell infiltration. Unsupervised transcriptomic analysis reveals five molecular clusters with distinct angiogenesis, stroma, proliferation and KRAS down signatures, which show association with fusion patterns and prognosis. In line with the aggressive nature, the high angiogenesis/stroma/proliferation cluster exclusively consists of tumors with ASPSCR1-TFE3 fusion. Here, we describe the genomic and transcriptomic features of TFE3-tRCC and provide insights into precision medicine for this disease.
Insights
This study reveals the complex molecular landscape of TFE3-translocation renal cell carcinoma (TFE3-tRCC), identifying aggressive subtypes and distinct molecular clusters. Findings offer insights for precision medicine in this rare kidney cancer.
Area of Science:
- Genomics
- Oncology
- Molecular Biology
Background:
- TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare kidney cancer subtype with limited treatment options for advanced stages.
- Understanding its molecular heterogeneity is crucial for developing targeted therapies.
Purpose of the Study:
- To comprehensively characterize the molecular features of untreated primary TFE3-tRCC.
- To identify genomic alterations and transcriptomic signatures associated with disease behavior and prognosis.
- To provide insights for precision medicine strategies.
Main Methods:
- Whole-exome sequencing
- RNA sequencing
- Unsupervised transcriptomic analysis
- Analysis of 63 untreated primary TFE3-tRCC samples
Main Results:
- TFE3-tRCC exhibits significant clinicopathological and genotypic heterogeneity.
- ASPSCR1-TFE3 fusion and loss of 22q are linked to aggressive features and poor outcomes.
- Five molecular clusters with distinct signatures (angiogenesis, stroma, proliferation, KRAS) were identified, correlating with fusion types and prognosis.
- Most TFE3-tRCCs show low PD-L1 expression and T-cell infiltration, except for MED15-TFE3 fusion tumors.
Conclusions:
- Genomic and transcriptomic profiling reveals distinct molecular subtypes within TFE3-tRCC.
- The ASPSCR1-TFE3 fusion is associated with a highly aggressive molecular profile.
- These findings pave the way for novel precision medicine approaches in TFE3-tRCC.
