Recurrent gene fusions are a unique class of genetic aberrations that are widespread and are the hallmark of several types of cancer. Currently known recurrent fusions, that were identified in prostate cancer phenotypes, involve erythroblastosis virus E26 transformation-specific (ETS) family transcription factors and their products are considered ‘undruggable’ by conventional approaches. However recently, rare targetable gene fusions involving the anaplastic lymphoma receptor tyrosine kinase (ALK) gene, were identified in lung cancers suggesting that similar gene fusions may occur in other epithelial cancers.
Rare targetable recurrent RAF gene fusions in advanced prostate cancer, gastric cancer and melanoma
Upon pursuing the observation of rare targetable gene fusions in lung cancer, researchers at the University of Michigan, identified two rare targetable recurrent RAF gene fusions in advanced prostate cancer, gastric cancer and melanoma. The two RAF gene fusions, SLC45A3-BRAF and ESRP1-RAF1, which were identified using paired-end transcriptome sequencing were sensitive to RAF and mitogen-activated protein kinase kinase (MAP2K1) inhibitors.
- Rare druggable recurrent gene fusions that function as diagnostic markers and clinical targets for cancer
- Diagnostic tool facilitating personalized cancer treatment and management
- Research tool (fusion genes) that induces neoplastic phenotype in cells and facilitates the study of their response to conventional drugs
- The identified gene fusions are druggable by conventional approaches, thereby greatly reducing costs associated with novel drug discovery process