BRAF Fusion Analysis in Pilocytic Astrocytomas: KIAA1549-BRAF 15-9 Fusions Are More Frequent in the Midline Than Within the Cerebellum

Faulkner, Claire; Ellis, Hayley Patricia; Shaw, Abigail; Penman, Catherine; Palmer, Abigail; Wragg, Christopher; Greenslade, Mark; Haynes, Harry Russell; Williams, Hannah; Lowis, Stephen; White, Paul; Williams, Maggie; Capper, David; Kurian, Kathreena Mary

Abstract

Copyright © 2015 by the American Association of Neuropathologists, Inc. Pilocytic astrocytomas (PAs) are increasingly tested for KIAA1549-BRAF fusions. We used reverse transcription polymerase chain reaction for the 3 most common KIAA1549-BRAF fusions, together with BRAF V600E and histone H3.3 K27M analyses to identify relationships of these molecular characteristics with clinical features in a cohort of 32 PA patients. In this group, the overall BRAF fusion detection rate was 24 (75%). Ten (42%) of the 24 had the 16-9 fusion, 8 (33%) had only the 15-9 fusion, and 1 (4%) of the patients had only the 16-11 fusion. In the PAs with only the 15-9 fusion, 1 PA was in the cerebellum and 7 were centered in the midline outside of the cerebellum, that is, in the hypothalamus (n = 4), optic pathways (n = 2), and brainstem (n = 1). Tumors within the cerebellum were negatively associated with fusion 15-9. Seven (22%) of the 32 patients had tumor-related deaths and 25 of the patients (78%) were alive between 2 and 14 years after initial biopsy. Age, sex, tumor location, 16-9 fusion, and 15-9 fusion were not associated with overall survival. Thus, in this small cohort, 15-9 KIAA1549-BRAF fusion was associated with midline PAs located outside of the cerebellum; these tumors, which are generally difficult to resect, are prone to recurrence.

• Journal Article Type: Article
• Publication Date: Jan 1, 2015
• Deposit Date: Aug 27, 2015
• Publicly Available Date: May 13, 2016
• Journal: Journal of Neuropathology and Experimental Neurology
• Print ISSN: 0022-3069
• Electronic ISSN: 1554-6578
• Publisher: Oxford University Press (OUP)
• Peer Reviewed: Peer Reviewed
• Volume: 74
• Issue: 9
• Pages: 867-872
• DOI: https://doi.org/10.1097/NEN.0000000000000226
• Keywords: BRAF, gene fusion, KIAA1549-BRAF, pilocytic astrocytoma, RT-PCR
• Public URL: https://uwe-repository.worktribe.com/output/828995
• Publisher URL: http://dx.doi.org/10.1097/NEN.0000000000000226
• Contract Date: May 13, 2016