BRAF Alterations Are Frequent in Cerebellar Low-Grade Astrocytomas With Diffuse Growth Pattern

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Low Grade Astrocytomas

Astrocytomas are tumors that are believed to arise from precursors of astrocytes – supportive cells of the brain named for their star-like shape. Astrocytomas are the most common of the primary brain tumors. The pathologist, using a microscope, grades these tumors on a scale of I to IV based on how quickly the cells are reproducing, as well as their potential to invade nearby tissue. Grade IV a...

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BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas.

The molecular pathogenesis of pediatric astrocytomas is still poorly understood. To further understand the genetic abnormalities associated with these tumors, we performed a genome-wide analysis of DNA copy number aberrations in pediatric low-grade astrocytomas by using array-based comparative genomic hybridization. Duplication of the BRAF protooncogene was the most frequent genomic aberration,...

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A brain-penetrant RAF dimer antagonist for the noncanonical BRAF oncoprotein of pediatric low-grade astrocytomas.

Background Activating mutations or structural rearrangements in BRAF are identified in roughly 75% of all pediatric low-grade astrocytomas (PLGAs). However, first-generation RAF inhibitors approved for adult melanoma have poor blood-brain penetrance and are only effective on tumors that express the canonical BRAFV600E oncoprotein, which functions as a monomer. These drugs (type I antagonists th...

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Effect of surgery on tumor progression and malignant degeneration in hemispheric diffuse low-grade astrocytomas.

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We recently reported that the vast majority (>90%) of low-grade diffuse gliomas (diffuse astrocytoma, oligoastrocytoma and oligodendroglioma) carry at least one of the following genetic alterations: IDH1/2 mutation, TP53 mutation or 1p/19q loss. Only 7% of cases were triple-negative (ie, lacking any of these alterations). In the present study, array comparative genomic hybridization (CGH) in 15...

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ژورنال

عنوان ژورنال: Journal of Neuropathology & Experimental Neurology

سال: 2012

ISSN: 0022-3069

DOI: 10.1097/nen.0b013e31825c448a