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Updated: Apr 11, 2026
Preparation of Formalin-fixed Paraffin-embedded Tissue Cores for both RNA and DNA Extraction
Published on: August 21, 2016
Identification of a novel PARP14-TFE3 gene fusion from 10-year-old FFPE tissue by RNA-seq
Weihua Huang1, Michael Goldfischer2, Sabina Babayeva1
1Department of Pathology, New York Medical College, Westchester Medical Center, Valhalla, NY.
Abstract:
Xp11 (TFE3) translocation renal cell carcinoma (RCC) is officially recognized as a distinct subtype of RCC in the 2004 WHO classification. This neoplasm is characterized by several chromosomal translocations between the TFE3-involving Xp11.2 breakpoint and various fusion partners. To date, five partner genes have been identified, that is, PRCC in 1q21, PSF in 1q34, ASPL in 17q25, CLTC in 17q23, and NONO in Xq12; and three additional translocations have been reported with no partner gene being defined: t(X;3)(p11;q23), t(X;10)(p11;q23), and t(X;19)(p11;q13). Here, we report the identification of a novel TFE3 fusion partner, PARP14 in chromosome band3q21. We used RNA-seq on a 10-year-old FFPE (formalin-fixed, paraffin-embedded) tissue sample, which carried t(X;3)(p11;q23) as detected in the original cytogenetic study. The fusion transcript connected the 5'-end of the first two exons of PARP14 to the 3'-end of five exons of TFE3, which was verified by reverse transcription PCR (RT-PCR) and Sanger sequencing. Similar to other TFE3 fusions previously reported, the predicted PARP14-TFE3 product retains the nuclear localization and DNA-binding domains of TFE3. This finding expands the list of TFE3 translocation partner genes and re-emphasizes the essential oncogenic role of TFE3 fusion proteins in this tumor. Our result also clearly demonstrated the feasibility of identifying chromosomal translocation by RNA-seq in clinical FFPE, which are easily accessible and associated with valuable clinical information. © 2015 Wiley Periodicals, Inc.
Insights
Researchers identified a new gene fusion partner, PARP14, in Xp11 translocation renal cell carcinoma (RCC). This discovery expands understanding of TFE3 fusion proteins
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Xp11 translocation renal cell carcinoma (RCC) is a distinct subtype characterized by TFE3 gene fusions.
- Five TFE3 partner genes (PRCC, PSF, ASPL, CLTC, NONO) and three undefined translocations are known.
Purpose of the Study:
- To identify novel TFE3 translocation partner genes in Xp11 translocation RCC.
- To demonstrate the utility of RNA-sequencing (RNA-seq) for detecting chromosomal translocations in FFPE samples.
Main Methods:
- RNA-sequencing was performed on a formalin-fixed, paraffin-embedded (FFPE) tissue sample with a known t(X;3)(p11;q23) translocation.
- Fusion transcript was identified and verified using reverse transcription PCR (RT-PCR) and Sanger sequencing.
Main Results:
- A novel TFE3 fusion partner gene, PARP14, was identified at chromosome band 3q21.
- The fusion transcript involved exons 1-2 of PARP14 and exons of TFE3, creating a predicted protein retaining TFE3's functional domains.
- RNA-seq successfully identified the chromosomal translocation in a clinical FFPE sample.
Conclusions:
- The identification of PARP14-TFE3 expands the known TFE3 translocation partners in Xp11 RCC.
- This finding reinforces the critical oncogenic role of TFE3 fusion proteins in this RCC subtype.
- RNA-seq is a feasible method for identifying chromosomal translocations in accessible FFPE tissues.
