Abstract
Recurrent fusions drive the pathogenesis of many hematological malignancies. Compared to routine cytogenetic/fluorescence in situ hybridization (FISH) studies, the RNA-based next-generation sequencing (NGS) fusion assay enables the identification of both known and novel fusions. In many cases, these recurrent fusions are crucial for diagnosis and are associated with prognosis, relapse prediction, and therapeutic options. The aim of this study is to investigate the application of the RNA-based NGS fusion assay in hematological malignancies. Our study included 3101 cases with available fusion results, and a fusion event was identified in 17.6% of cases. The discordant rate between the RNA-based NGS fusion assay and cytogenetic/FISH studies was 36.3%. Further analysis of discordant cases indicated that, compared to cytogenetic/FISH studies, the RNA-based NGS fusion assay significantly improved the identification of cryptic fusion genes, such as NUP98::NSD1, P2RY8::CRLF2, and KMT2A fusions involving different partners. Additionally, our study identified 24 novel fusions and 16 cases with the simultaneous presence of two fusions. These additional findings from the RNA-based NGS fusion assay resulted in improved risk stratification, disease targeting and monitoring. In conclusion, our study demonstrates the feasibility and utility of an RNA-based NGS fusion assay for patients with hematological malignancies, suggesting that it may be essential for the routine clinical workup of these patients.