Narrative review of molecular pathways of kinase fusions and diagnostic approaches for their detection in non-small cell lung carcinomas
Matthias S. Matter, Obinna Chijioke, Spasenija Savic, Lukas Bubendorf
Abstract
. All these fusions involve tyrosine kinases (TK), which are activated due to structural rearrangements on the DNA level. Although the overall prevalence of these fusions in LUAD is rare, their detection is extremely important, as they are linked to an excellent response to TK inhibitors. Therefore, reliable screening methods applicable to small tumor samples (biopsies and cytology specimens) are required in the diagnostic workup of advanced NSCLC. Several methods are at disposal in a routine laboratory to demonstrate, directly or indirectly, the presence of a gene fusion. These methods include immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR), multiplex digital color-coded barcode technology or next-generation sequencing (NGS) either on DNA or RNA level. In our review, we will summarize the increasing number of relevant fusion genes in NSCLC, point out their underlining molecular mechanisms and discuss different methods for the detection of fusion genes.