Practical Considerations for Oncogenic Fusion Detection and Reporting in Solid Tumors

Chromosomal rearrangements that result in oncogenic fusions can hold tremendous clinical significance in solid tumors, often with diagnostic or treatment implications.

Traditionally, low-throughput methods such as fluorescence in situ hybridization were used to identify fusions in the clinical laboratory. With the rise of next-generation sequencing techniques and the broad adoption of comprehensive genomic profiling, the practice of screening for fusions as part of an oncologic workup has evolved. RNA sequencing methods are increasingly used, as these comprehensive high-throughput assays have many advantages over traditional techniques. Several RNA sequencing platforms are available, each with benefits and drawbacks. Regardless of the approach, systematic evaluation of the RNA sequencing results and the fusions identified by the assay should be performed. Assessment of fusion events relies upon evaluation of quality evidence, structural evidence, and functional evidence to ensure accurate fusion reporting and interpretation.

Given the clinical significance of gene fusions in oncology, understanding the variety of assays available for fusion detection, their benefits and drawbacks, and how they are used in the identification and interpretation of gene fusions is important for the modern precision oncology practice.