Identification of a novel KIF13A-RET fusion in lung adenocarcinoma by next-generation sequencing

Abstract

RET fusions have been reported in 1-2% of lung adenocarcinomas, and represent an actionable target. Patients whose tumors possess RET fusion are associated with clinical benefit from the treatment with multi-kinase inhibitors such as cabozantinib and vandetanib. Further molecular screening for RET fusions is warranted. Novel KIF13A-RET fusion containing an intact RET kinase domain involving exons 1-18 of KIF13A and exons 12-20 of RET was identified in a lung cancer specimen from an 74-year-old Asian never smoker by next-generation sequencing (NGS) during clinical care. The patient was negative for EGFR, ALK, ROS1 and other putative driver alterations. Fusion analysis is consistent with other described RET fusions and is predicted to result in aberrant constitutive activation caused by dimerization and sensitivity to RET-directed therapies. We describe a novel RET-fusion with molecular characteristics consistent with RET-driven non-small cell lung cancer. Our case expands the spectrum of RET fusion partners and supports broad molecular profiling in non-small cell lung cancer optimizing patient therapeutic options. The new RET fusion has immediate clinical implications for cancer patients.

Keywords: Lung adenocarcinoma; Next generation sequencing; RET fusion; Targeted therapy.