We have explored novel fusion genes in solid cancers and have identified 10 fusion genes thus far. Receptor tyrosine kinases are primarily chosen as a target of study because kinase aberrations are targetable and therefore the patients with the aberrations benefit from inhibitor therapies. In fact, the newly identified kinase fusions are all driver mutations and targetable. The exploring system we are using for this project is based on histopathology and is therefore a unique system. The methods used in this system can also be used for routine diagnosis, leading to the development of novel diagnostics. Several methods developed for exploring ALK fusion genes are commercially available as diagnostic methods and have been used for selecting patients for an ALK inhibitor clinical trial.
FISH assays for EML4-ALK fusion gene in lung adenocarcinoma tissue
In the fusion assay (left), EML4 and ALK genes are labeled red and green, respectively. EML4-ALK fusion gene appears yellow. The right panel shows the split assay for the ALK gene in the same case. The upstream and downstream of the ALK gene are labeled red and green, respectively. If the ALK gene is translocated, the signals appear separated.