Identification of Novel Fusion Transcripts in Undifferentiated Pleomorphic Sarcomas by Transcriptome Sequencing

Abstract

Background/aim: Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal neoplasm characterized by chromosomal instability. The aim of this study was to identify fusion events involved in UPS.

Materials and methods: Transcriptome sequencing was performed to search for new fusion genes in 19 UPS samples, including two paired recurrent (R) and re-recurrent (RR) samples.

Results: A total of 66 fusion genes were detected. Among them, 10 novel fusion genes were further confirmed by reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing. Retinoblastoma (RB1) fusions (2 cases) were the most recurrent fusion genes. The gene fusions RB1-RNASEH2B, RB1-FGF14-AS1, and E2F6-FKBP4 were correlated with the Rb/E2F pathway. Pseudogenes were involved in the formation of the gene fusions CIC-DUX4L8 and EIF2AK4-ANXA2P2. Importantly, targetable gene fusions (PDGFRA-MACROD2 and NCOR1-MAP2K1) were detected in UPS.

Conclusion: Screening for the presence of fusion transcripts will provide vital clues to the understanding of genetic alterations and the finding of new targeted therapies for UPS.

Keywords: RB1; Soft tissue sarcoma; fusion gene; pseudogene; targetable fusion; transcriptome sequencing; undifferentiated pleomorphic sarcoma.