BRAF alterations in primary glial and glioneuronal neoplasms of the central nervous system with identification of 2 novel KIAA1549:BRAF fusion variants.

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 BRAF mutations in 8% of tumors. BRAF 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.

authors

Lin A,Rodriguez FJ,Karajannis MA,Williams SC,Legault G,Zagzag D,Burger PC,Allen JC,Eberhart CG,Bar EE

doi

10.1097/NEN.0b013e31823f2cb0

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

66-72

issue

1

eissn

0022-3069

issn

1554-6578

journal_volume

71

pub_type

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