These authors contributed equally to this work.
Recurrent BRAF kinase fusions in melanocytic tumors offer an opportunity for targeted therapy
Article first published online: 19 AUG 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Pigment Cell & Melanoma Research
Volume 26, Issue 6, pages 845–851, November 2013
How to Cite
Botton, T., Yeh, I., Nelson, T., Vemula, S. S., Sparatta, A., Garrido, M. C., Allegra, M., Rocchi, S., Bahadoran, P., McCalmont, T. H., LeBoit, P. E., Burton, E. A., Bollag, G., Ballotti, R. and Bastian, B. C. (2013), Recurrent BRAF kinase fusions in melanocytic tumors offer an opportunity for targeted therapy. Pigment Cell & Melanoma Research, 26: 845–851. doi: 10.1111/pcmr.12148
- Issue published online: 24 OCT 2013
- Article first published online: 19 AUG 2013
- Accepted manuscript online: 24 JUL 2013 08:50AM EST
- Manuscript Accepted: 19 JUL 2013
- Manuscript Received: 10 JUN 2013
- National Institutes of Health. Grant Numbers: R01 CA131524, P01 CA025874
- BRAF ;
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 BRAFV600E 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.