Skip Navigation LinksHome > January 2012 - Volume 71 - Issue 1 > BRAF Alterations in Primary Glial and Glioneuronal Neoplasms...
Journal of Neuropathology & Experimental Neurology:
doi: 10.1097/NEN.0b013e31823f2cb0
Original Articles

BRAF Alterations in Primary Glial and Glioneuronal Neoplasms of the Central Nervous System With Identification of 2 Novel KIAA1549: BRAF Fusion Variants

Lin, Alex MS; Rodriguez, Fausto J. MD; Karajannis, Matthias A. MD; Williams, Susan C. MD; Legault, Genevieve MD; Zagzag, David MD, PhD; Burger, Peter C. MD; Allen, Jeffrey C. MD; Eberhart, Charles G. MD, PhD; Bar, Eli E. PhD

Supplemental Author Material
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Abstract

Abstract: Recent studies highlight the importance of BRAF alterations resulting in mitogen activated protein kinase (MAK/ERK) pathway activation in low-grade CNS tumors. We studied 106 low-grade CNS neoplasms in a cohort of primarily pediatric patients to identify the prevalence and clinicopathologic significance of these alterations. Polymerase chain reaction testing identified KIAA1549:BRAF fusions in 51 (48%) tumors overall, including 42 (60%) pilocytic astrocytomas, 4 (17%) unclassifiable low-grade gliomas, 4 (36%) low-grade glioneuronal/neuroepithelial tumors, 0 (of 5) pleomorphic xanthoastrocytomas, 0 (of 4) diffuse astrocytomas (World Health Organization grade II), and 1 (of 3, 33%) pilomyxoid astrocytoma. KIAA1549:BRAF gene fusions confirmed by sequencing included the previously reported ones involving exons 1–16/9–18 (49%), 1–15/9–18 (35%), and 1–16/11–18 (8%) and 2 fusions with novel breakpoints: 1–15/11–18 (6%) and 1–17/10–18 (1%). DNA sequencing identified BRAFV600E mutations in 8% of tumors. BRAFG468A mutations were absent. KIAA1549:BRAF fusions were significantly more frequent in infratentorial (57%) and optic pathway (59%) tumors versus supratentorial (19%) tumors (p = 0.001). We did not identify significantly improved progression-free survival in tumors with fusions. In summary, KIAA1549:BRAF fusions predominate in pilocytic astrocytomas but are also present in some low-grade unclassifiable gliomas and glioneuronal tumors. The prognostic and therapeutic significance of this alteration is unclear and merits further study.

© 2012 American Association of Neuropathologists, Inc

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