Chromosome Band 7q34 Deletions Resulting in KIAA1549‐BRAF and FAM131B‐BRAF Fusions in Pediatric Low‐Grade Gliomas. (12th September 2014)

• Record Type: Journal Article
• Authors: Roth, Jacquelyn J.; Santi, Mariarita; Pollock, Avrum N.; Harding, Brian N.; Rorke‐Adams, Lucy B.; Tooke, Laura S.; Biegel, Jaclyn A.
• Is Part Of: Brain pathology. Volume 25:Number 2(2015:Mar.)
• Page Start: 182
• Page End: 192
• Publication Date: 2014-09-12
• Subjects: Nervous system -- Diseases -- Periodicals; Brain -- Diseases -- Periodicals; Neurology -- Periodicals; Brain Diseases -- Periodicals; Cerveau -- Maladies -- Périodiques; Système nerveux -- Maladies -- Périodiques; Neurologie -- Périodiques; 616.805
• DOI: 10.1111/bpa.12167
• Languages: English
• ISSNs: 1015-6305

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>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 <italic>BRAF</italic> mutations, inactivation of <italic>NF</italic><italic>1</italic>, and <italic>KIAA</italic><italic>1549‐</italic><italic>BRAF</italic> and <italic>FAM</italic><italic>131</italic><italic>B</italic><italic>‐</italic><italic>BRAF</italic> fusions. The <italic>KIAA</italic><italic>1549‐</italic><italic>BRAF</italic> 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 <italic>BRAF</italic> fusion. Case 1 was likely a pilocytic astrocytoma (PA) with three deletions in 7q33q34 and an exon 15‐9 <italic>KIAA</italic><italic>1549‐</italic><italic>BRAF</italic> 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 <italic>BRAF</italic> and extended to the 3′ end of <italic>FAM</italic><italic>131</italic><italic>B</italic>. In case 3, deletions involving <italic>BRAF</italic> and <italic>FAM</italic><italic>131</italic><italic>B</italic> were observed in both a primary and a recurrent PA. RNA‐based sequence analysis of cases 2 and 3 confirmed a fusion between <italic>FAM</italic><italic>131</italic><italic>B</italic> exon 2 and <italic>BRAF</italic> 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. <italic>BRAF</italic> fusions can result from multiple non‐overlapping deletions, suggesting various complex mechanisms of formation.</p> </abstract>