Beyond chromosomal rearrangements: The expanding landscape of gene fusions and chimeric RNAs

BCR–ABL, the pioneering gene fusion resulting from chromosomal translocation, has marked a major milestone in understanding genetic alterations in cancer. Initially, gene fusions were linked solely to chromosomal rearrangements, serving as diagnostic markers and cancer drivers. However, advancements in high-throughput sequencing and bioinformatics have revealed additional mechanisms underlying gene fusion. The term “gene fusion” primarily refers to fusion events at the DNA level, whereas “chimeric RNA” encompasses a wide range of transcripts containing exons from different parental genes, including gene fusion transcripts. Recent developments have identified numerous chimeric RNAs in various cancer types, extending even to non-cancerous tissues. Chimeric RNAs, originating from events such as trans-splicing, read-through, and intergenic splicing, form a complex landscape with varied functions. While some chimeric RNAs have defined roles and therapeutic potential, a comprehensive understanding of their diverse functions remains a priority. Exploring the full spectrum of chimeric RNA activities is crucial for revealing their clinical and therapeutic implications. In addition, chimeric RNAs are key players in tumorigenesis, affecting cellular processes, and driving cancer progression. Understanding their intricate interactions with cellular pathways is essential for developing targeted therapies and precision medicine approaches. The dynamic nature of chimeric RNAs highlights the need for ongoing research to fully harness their diagnostic and therapeutic potential.