Abstract 332P
Background
Translocation renal cell carcinoma (TRCC) is predominantly observed in children and young adults. It is characterized by higher tumor invasiveness and a poorer prognosis compared to other forms, and there is a notable lack of effective therapeutic targets.
Methods
This study integrated retrospective molecular data from multiple TRCC cohorts, comprising genomic (n=149), transcriptomic (n=92), and proteomic (n=74) datasets. Genomic analyses included mapping TRCC genomes to identify potential driver mutations. Transcriptomic and proteomic investigations focused on distinguishing molecular discrepancies between TRCC and non-TRCC cases, as well as delineating the molecular variances and associated oncogenic pathways linked to different gene fusion types in TRCC, with fusion partners including ASPSCR1, SFPQ, NONO, PRCC, MED15, and RBM10.
Results
Genomic mapping revealed potential oncogenes specific to TRCC, such as PCLO, BCDIN3D, and NDRG1—distinct from genes associated with clear cell, papillary, and chromophobe renal cell carcinoma. Transcriptomic and proteomic analyses indicated significant activation of ERK signaling and tumor necrosis factor production signaling pathways in TRCC compared to non-TRCC. The TFE3-RBM10 fusion was associated with pronounced activation of mTOR and ERK signaling pathways. TFE3-PRCC fusion exhibited elevated JAK-STAT and inflammatory response signals, suggesting potential benefits from immunotherapy. Fusions such as TFE3-SFPQ, TFE3-MED15, and TFE3-NONO were linked to pathways like VEGF and FGF, indicating potential efficacy of TKI drugs. Notably, the TFE3-ASPSCR1 fusion type, characterized by significantly elevated hypoxia, mTOR, and JAK-STAT signals, suggested that targeting angiogenesis alone may not sufficiently inhibit tumor progression in this subtype.
Conclusions
Significant biological differences exist between TRCC and non-TRCC, with various fusion types in TRCC corresponding to unique biological behaviors and therapeutic targets. This study underscores the importance of personalized treatment strategies in managing TRCC based on specific molecular profiles.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Fudan University Shanghai Cancer Center.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.