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, 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 SLC45A3-BRAF, Rare targetable recurrent androgen responsive RAF gene fusions in advanced prostate cancer
To search for druggable targets in prostate cancer, researchers at the University of Michigan, performed paired-end transcriptome sequencing of ETS rearrangement-negative prostrate cancers. They observed a interchromosomal rearrangement resulting in the fusion of untranslated exon 1 of SLC45A3 which is a prostate-specific, androgen responsive gene, with exon 8 of BRAF which is the raf murine sarcoma viral oncogene homolog B1. Expression of SLC45A3-BRAF fusion gene in prostate cells induced a neoplastic phenotype that was sensitive to RAF and mitogen-activated protein kinase kinase (MAP2K1) inhibitors.
- Rare druggable recurrent gene fusion that function as diagnostic marker and clinical target for prostate cancer
- Diagnostic tool facilitating personalized prostate cancer treatment and management
- Research tool (SLC45A3-BRAF) that induces neoplastic phenotype in prostate cells and facilitates the study of their response to conventional drugs
- The identified gene fusion is druggable by conventional approaches, thereby greatly reducing costs associated with novel drug discovery process