Gene fusion

Gene fusions are genomic events where two previously separate genes become joined, typically via chromosomal translocation, inversion, or deletion. These occurrences frequently create chimeric genes that encode fusion proteins with aberrant properties, such as constitutive kinase activity or deregulated transcription [1, 5]. In oncology, gene fusions like BCR-ABL1 and EML4-ALK act as potent driver mutations that promote uncontrolled cell growth and survival [7, 12]. They are particularly significant in precision medicine as they provide highly specific therapeutic targets for small-molecule inhibitors [8, 11]. For instance, tyrosine kinase inhibitors (TKIs) like imatinib and larotrectinib are designed to specifically block the signaling pathways activated by these fusion proteins [8, 13]. While these treatments often lead to high response rates, the long-term efficacy is frequently limited by the emergence of resistance mutations within the fusion gene [6, 12]. Detecting gene fusion occurrences via advanced molecular techniques like next-generation sequencing is essential for patient stratification and monitoring [3, 5].

Other names

Chimeric geneChromosomal translocationGene rearrangementFusion transcriptGenomic fusion

Small-molecule inhibition of the chimeric protein's enzymatic activity (typically tyrosine kinase activity) or targeting downstream signaling pathways.