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A renal cell carcinoma with EWSR1-TFE3 fusion gene
Xing-Ping Lang1, Jian Pan2, Chun-Xiao Yang1
1Suzhou Sano Precision Medicine Ltd, Suzhou, China.
Abstract:
Both EWSR1 and TFE3 are well-known oncogenes. EWSR1 encodes an RNA-binding protein involved in multiple soft tissue tumors, including Ewing's sarcoma/peripheral neuroectodermal tumor, desmoplastic small round cell tumor, soft tissue clear cell sarcoma (malignant melanoma of soft parts), extraskeletal myxoid chondrosarcoma, and myxoid liposarcomas. TFE3 regulates both Golgi and lysosomal homeostasis and is rearranged in renal cell carcinoma (RCC), alveolar soft part sarcoma, epithelioid hemangioendothelioma, and perivascular epitheloid cell tumors (PEComas). In this report, we found a rare case of RCC with a fusion between 5' EWSR1 and 3' TFE3. The fusion product retained most functional motifs of TFE3. The oncogenic mechanism likely involves TFE3 overexpression through its juxtaposition with the regulatory elements of EWSR1 and its translocation to the nucleus, resulting in the deregulation of Golgi and lysosomal homeostasis. This is a second case of RCC containing EWSR1-TFE3 fusion.
Insights
A rare EWSR1-TFE3 gene fusion was identified in renal cell carcinoma (RCC). This oncogenic mechanism likely drives RCC development by disrupting cellular homeostasis.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- EWSR1 and TFE3 are established oncogenes implicated in various cancers.
- EWSR1 is an RNA-binding protein involved in soft tissue tumors.
- TFE3 regulates Golgi and lysosomal homeostasis and is altered in renal cell carcinoma (RCC) and other tumors.
Observation:
- A rare case of RCC presented with a fusion between the EWSR1 and TFE3 genes.
- The resulting EWSR1-TFE3 fusion product preserved critical functional motifs of TFE3.
Findings:
- The oncogenic mechanism involves EWSR1 regulatory elements driving TFE3 overexpression.
- Translocation of the fusion protein to the nucleus disrupts Golgi and lysosomal homeostasis.
- This represents the second documented instance of EWSR1-TFE3 fusion in RCC.
Implications:
- Understanding this rare fusion provides insights into novel oncogenic pathways in RCC.
- The findings may contribute to developing targeted therapies for specific RCC subtypes.
- Further research into EWSR1-TFE3 driven tumorigenesis is warranted.
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