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

• Published in: Journal of neuropathology and experimental neurology Vol. 74; no. 9; pp. 867 - 872
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England American Association of Neuropathologists, Inc 01.09.2015; by American Association of Neuropathologists, Inc; American Association of Neuropathologists
• Subjects: Adolescent; Astrocytoma - diagnosis; Astrocytoma - genetics; Cerebellar Neoplasms - diagnosis; Cerebellar Neoplasms - genetics; Cerebellum - pathology; Child; Child, Preschool; Cohort Studies; Female; Follow-Up Studies; Gene Fusion - genetics; Humans; Infant; Male; Original; Proto-Oncogene Proteins B-raf - genetics; RT-PCR; Gene fusion; Pilocytic astrocytoma
• ISSN: 0022-3069; 1554-6578; 1554-6578
• DOI: 10.1097/NEN.0000000000000226

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.