title: BRAF Fusion Analysis in Pilocytic Astrocytomas: KIAA1549-BRAF 15-9 Fusions Are More Frequent in the Midline Than Within the Cerebellum.
abstract: 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.
authors.affiliation: From the Bristol Genetics Laboratory, Pathology Sciences, Southmead Hospital, Bristol (CF, AP, CW, MG, MW); Brain Tumour Research Group, Institute of Clinical Neurosciences, Southmead Hospital (HPE, AS, CP, HRH, HW, KMK); Department of Paediatric Oncology, Bristol Royal Hospital for Children (SL); and Applied Statistics Group, University of the West of England (PW), Bristol, UK; and Department of Neuropathology, Institute of Pathology, University of Heidelberg and CCU Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Claire
authors.initials: C
authors.lastname: Faulkner
authors.forename: Hayley Patricia
authors.initials: HP
authors.lastname: Ellis
authors.forename: Abigail
authors.initials: A
authors.lastname: Shaw
authors.forename: Catherine
authors.initials: C
authors.lastname: Penman
authors.forename: Abigail
authors.initials: A
authors.lastname: Palmer
authors.forename: Christopher
authors.initials: C
authors.lastname: Wragg
authors.forename: Mark
authors.initials: M
authors.lastname: Greenslade
authors.forename: Harry Russell
authors.initials: HR
authors.lastname: Haynes
authors.forename: Hannah
authors.initials: H
authors.lastname: Williams
authors.forename: Stephen
authors.initials: S
authors.lastname: Lowis
authors.forename: Paul
authors.initials: P
authors.lastname: White
authors.forename: Maggie
authors.initials: M
authors.lastname: Williams
authors.forename: David
authors.initials: D
authors.lastname: Capper
authors.forename: Kathreena Mary
authors.initials: KM
authors.lastname: Kurian
mesh_terms: D000293:Adolescent; D001254:Astrocytoma / Q000175:diagnosis* / Q000235:genetics*; D002528:Cerebellar Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D002531:Cerebellum / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D050939:Gene Fusion / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf