Molecules of lung cancer - fusion alterations in nonsmall cell lung cancer: biology and diagnostic considerations.

Fusion alterations have transformed outcomes for a subset of patients with nonsmall cell lung cancer (NSCLC), as part of the evolution of precision oncology. While the role of molecular pathology in the diagnosis and treatment of NSCLC has rapidly evolved, it remains the responsibility of the pulmonologist to coordinate the diagnostic evaluation of patients with lung cancer, including clinical assessment, obtaining a histological diagnosis and coordination of staging procedures. This review focuses on the biology, clinical significance and diagnostic considerations of fusion alterations in NSCLC. We summarise current knowledge regarding the role of actionable gene fusion translocations, including anaplastic lymphoma kinase (ALK), ros-protooncogene 1 (ROS1), retinoblastoma rearranged during transfection (RET) and neurotrophic tyrosine receptor kinase (NTRK) fusions, while outlining clinical decision-making considerations and testing frameworks. For respiratory physicians, it is essential to prioritise suitable diagnostic modalities by taking into account tissue availability, turnaround time, and consideration of next generation sampling methods and noninvasive sampling such as blood-based circulating tumour DNA assays.