title: Chromosome band 7q34 deletions resulting in KIAA1549-BRAF and FAM131B-BRAF fusions in pediatric low-grade Gliomas.
abstract: The majority of pediatric low-grade gliomas (LGGs) are characterized by constitutive activation of the mitogen-activated protein kinase (MAPK) pathway through various mechanisms including BRAF mutations, inactivation of NF1, and KIAA1549-BRAF and FAM131B-BRAF fusions. The KIAA1549-BRAF fusion typically results from a 2.0 Mb tandem duplication in chromosome band 7q34. In the present study, single nucleotide polymorphism (SNP)-based array analysis of three LGGs demonstrated deletions in 7q34 that resulted in a BRAF fusion. Case 1 was likely a pilocytic astrocytoma (PA) with three deletions in 7q33q34 and an exon 15-9 KIAA1549-BRAF fusion. SNP array analysis of case 2, a possible dysembryoplastic neuroepithelial tumor (DNT), revealed a 2.6 Mb deletion, which included the 5' end of BRAF and extended to the 3' end of FAM131B. In case 3, deletions involving BRAF and FAM131B were observed in both a primary and a recurrent PA. RNA-based sequence analysis of cases 2 and 3 confirmed a fusion between FAM131B exon 2 and BRAF exon 9. The presence of fusion transcripts in these three LGGs highlights the utility of SNP array analysis to identify deletions that are suggestive of fusion proteins. BRAF fusions can result from multiple non-overlapping deletions, suggesting various complex mechanisms of formation.
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Jacquelyn J
authors.initials: JJ
authors.lastname: Roth
authors.forename: Mariarita
authors.initials: M
authors.lastname: Santi
authors.forename: Avrum N
authors.initials: AN
authors.lastname: Pollock
authors.forename: Brian N
authors.initials: BN
authors.lastname: Harding
authors.forename: Lucy B
authors.initials: LB
authors.lastname: Rorke-Adams
authors.forename: Laura S
authors.initials: LS
authors.lastname: Tooke
authors.forename: Jaclyn A
authors.initials: JA
authors.lastname: Biegel
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: D015514:Oncogene Proteins, Fusion; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; FAM131B; KIAA1549; pediatric glioma