Pediatric glioma-associated KIAA1549: BRAF expression regulates neuroglial cell growth in a cell type-specific and mTOR-dependent manner

Aparna Kaul, Yi Hsien Chen, Ryan J. Emnett, Sonika Dahiya, David H. Gutmann

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Tandem duplications involving the BRAF kinase gene have recently been identified as the most frequent genetic alteration in sporadic pediatric glioma, creating a novel fusion protein (f-BRAF) with increased BRAF activity. To define the role of f-BRAF in gliomagenesis, we demonstrate that f-BRAF regulates neural stem cell (NSC), but not astrocyte, proliferation and is sufficient to induce glioma-like lesions in mice. Moreover, f-BRAF-driven NSC proliferation results from tuberin/Rheb-mediated mammalian target of rapamycin (mTOR) hyperactivation, leading to S6-kinase-dependent degradation of p27. Collectively, these results establish mTOR pathway activation as a key growth regulatory mechanism common to both sporadic and familial low-grade gliomas in children.

Original languageEnglish
Pages (from-to)2561-2566
Number of pages6
JournalGenes and Development
Volume26
Issue number23
DOIs
StatePublished - Dec 2012

Keywords

  • Astrocytes
  • Neural stem cells
  • Pilocytic astrocytoma

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