Cancers with Kinase Fusion Exhibit Fewer Actionable Alterations Than Those with Kinase Mutation and Amplification

Abstract Background Kinase-related gene fusion and point mutations are important drivers, and optimized targeted therapy against these alterations is required. The effects of molecularly targeted therapeutics vary depending on the alteration, and such therapeutics have achieved their greatest success when used to treat chronic myelogenous leukemia with kinase fusion protein. In this study, we aimed to compare the numbers of actionable alterations in patients with kinase domain fusions, mutations, and amplifications. Methods To detect gene-fusion events, we analyzed 456 patients with 31 solid cancer types who visited our division between June 2020 and May 2023. We performed comprehensive genomic sequencing using FoundationOne® CDx (F1CDx) and FoundationOne® Liquid CDx (F1LCDx) to detect alterations involving multiple-fusion calling, and compared the number of actionable alterations in patients with kinase-domain fusions and mutations. The significance of these gene alterations was analyzed at a team conference. Results Among the 418 patients, we identified 44 with kinase-domain fusions, and F1CDx and F1LCDx detected 12 with kinase-domain fusions. We identified 78 patients with kinase-domain mutations and 33 with amplifications. The numbers of actionable alterations in patients with kinase-domain fusion, mutation, or amplification (median [IQR]) were 2 (0–3.5), 5 (4–7), and 5.5 (4.25–7.5), respectively. Patients with kinase fusion had significantly fewer actionable alterations than those with kinase-domain mutations and amplifications. However, those cancers with fusion involving tumor suppressors tended to have more passenger alterations (4 [2–9.75]; median [IQR]). Conclusions Cancers with kinase fusions tended to exhibit fewer actionable alterations than those with kinase mutations and amplifications. These findings indicate that kinase fusions are strong drivers of cancer development. In particular, kinase fusions in cancer are considered ideal targets for molecular therapeutics.