A novel VCP::TFE3 gene fusion resulting from t(X;9)(p11.23;p13.3) chromosome translocation in TFE3 rearranged renal cancer cell carcinoma.

Renal cell carcinoma with rearrangement of TFE3 (Transcription Factor for Immunoglobulin Heavy-Chain Enhancer 3) (TFE3-rearranged RCC) at Xp11.2 is a rare tumor entity but the most frequent among the MiT (Microphthalmia Transcription Factor) family translocation renal cell carcinomas. Here, we report the identification of a new VCP::TFE3 fusion gene as the result of a t(X;9)(p11.23;p13.3) translocation identified by Whole Transcriptome Sequencing. No other relevant molecular alteration was identified by Whole Exome Sequencing. This case showed typical morphological features of TFE3-rearranged RCC with positive TFE3 immunostaining and positive TFE3 break-apart FISH. MET was also overexpressed on immunohistochemistry. The patient had metastatic disease and was treated by surgery and five lines of therapy, including 24 months of stable disease on the MET inhibitor cabozantinib, with an overall survival of 7 years. In addition to expanding the spectrum of TFE3 rearrangement partners, this report highlights the complexity of these tumors and supports the development of translational programs in renal cancer. This article is protected by copyright. All rights reserved.