Journal
CANCER RESEARCH
Volume 68, Issue 21, Pages 8673-8677Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-08-2097
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Funding
- Samantha Dickson Brain Tumour Trust
- Cancer Research UK
- Jacqueline Seroussi Memorial Foundation for Cancer Research
- Cambridge Fund for the Prevention of Disease
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Brain tumors are the most common solid tumors of childhood, and pilocytic astrocytomas (PA) are the most common central nervous system tumor in 5 to 19 year olds. Little is known about the genetic alterations underlying their development. Here, we describe a tandem duplication of similar to 2 Mb at 7q34 occurring in 66% of As. This rearrangement, which was not observed in a series of 244 higher-grade astrocytomas, results in an in-frame fusion gene incorporating the kinase domain of the BRAF oncogene. We further show that the resulting fusion protein has constitutive BRAF kinase activity and is able to transform NIH3T3 cells. This is the first report of BRAF activation through rearrangement as a frequent feature in a sporadic tumor. The frequency and specificity of this change underline its potential both as a therapeutic target and as a diagnostic tool. [Cancer Res 2008;68(21):8673-7]
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