Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas
By David T. W. Jones, S. Kocialkowski, Lu Liu, D. Pearson, L. M. Bäcklund, K. Ichimura, V. Collins. Cancer Research, 2008
861 citations recorded by the source corpus.
Brain tumours are the commonest solid tumours of childhood, and pilocytic astrocytomas (PAs) are the most common central nervous system tumour in 5-19 year-olds. Little is known about the genetic alterations underlying their development. Here we describe a tandem duplication of ∼2Mb at 7q34 occurring in 66% of pilocytic astrocytomas. 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 a diagnostic tool.
Subfields: Genetics, Neurology, Ophthalmology
View Paper: https://www.semanticscholar.org/paper/e5e3c439ba7e3222d6a259568f4e3be2f0ead268
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In Genetics
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Citations in the corpus
- Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma (2011, background): “[12, 17, 19, 32, 40] as a relatively high proportion of extra-”
- Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma (2013, neutral): “Genetic alterations within the MAPK signaling pathway are a hallmark of this tumor, with KIAA1549 - BRAF fusion being the most frequent event 6–8 .”
- Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. (2018, positive): “…mCRPC. Duplications Target AR, MYC, and FOXA1 Genomic duplication events are a mechanism of genome evolution (Ohno, 1970) and are known to alter specific drivers important in cancer, such as FLT3 in acute myeloid leukemia and BRAF in pilocytic astrocytoma (Jones et al., 2008; Nakao et al., 1996).”