BRAF is the most prevalent oncogene and an important therapeutic target in 
melanoma. In some cancers, BRAF is activated by rearrangements that fuse its 
kinase domain to 5' partner genes. We examined 848 comparative genomic 
hybridization profiles of melanocytic tumors and found copy number transitions 
within BRAF in 10 tumors, of which six could be further characterized by 
sequencing. In all, the BRAF kinase domain was fused in-frame to six N-terminal 
partners. No other mutations were identified in melanoma oncogenes. One of the 
seven melanoma cell lines without known oncogenic mutations harbored a similar 
BRAF fusion, which constitutively activated the MAP kinase pathway. Sorafenib, 
but not vemurafenib, could block MAP kinase pathway activation and proliferation 
of the cell line at clinically relevant concentrations, whereas BRAF(V) (600E) 
mutant melanoma cell lines were significantly more sensitive to vemurafenib. The 
patient from whom the cell line was derived showed a durable clinical response 
to sorafenib.