The fusion landscape of hepatocellular carcinoma

Abstract

Most cases of hepatocellular carcinoma (HCC) are already advanced at the time of diagnosis, which limits treatment options. Challenges in early-stage diagnosis may be due to the genetic complexity of HCC. Gene fusion plays a critical function in tumorigenesis and cancer progression in multiple cancers, yet the identities of fusion genes as potential diagnostic markers in HCC have not been investigated. Here, we employed STAR-Fusion and identified 43 recurrent fusion events in our own and four public RNA-seq datasets. We identified 2354 different gene fusions in two hepatitis B virus (HBV)-HCC patients. Validation analysis against the four RNA-seq datasets revealed that only 1.8% (43/2354) were recurrent fusions. Comparison with the four fusion databases demonstrated that 19 recurrent fusions were not previously annotated to diseases and three were annotated as disease-related fusion events. Finally, we validated six of the novel fusion events, including RP11-476K15.1-CTD-2015H3.2, by RT-PCR and Sanger sequencing of 14 pairs of HBV-related HCC samples. In summary, our study provides new insights into gene fusions in HCC and may contribute to the development of anti-HCC therapy.