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01-12-2010 | Original Paper

MYB upregulation and genetic aberrations in a subset of pediatric low-grade gliomas

Authors: Ruth G. Tatevossian, Bo Tang, James Dalton, Tim Forshew, Andrew R. Lawson, Jing Ma, Geoff Neale, Sheila A. Shurtleff, Simon Bailey, Amar Gajjar, Suzanne J. Baker, Denise Sheer, David W. Ellison

Published in: Acta Neuropathologica | Issue 6/2010

Abstract

Recent studies of genetic abnormalities in pediatric low-grade gliomas (LGGs) have focused on activation of the ERK/MAPK pathway by KIAA1549-BRAF gene fusions in the majority of pilocytic astrocytomas (PAs) and by rare mutations in elements of the pathway across histopathologically diverse LGGs. This study reports that MYB, an oncogene not previously implicated in gliomagenesis, is activated in a diverse subset of pediatric LGGs. The study cohort comprised 57 pediatric LGGs and a comparative cohort of 59 pediatric high-grade gliomas (HGGs). The LGG cohort included 34 PAs and 23 diffuse gliomas; fibrillary astrocytomas (n = 14), oligodendroglial tumors (n = 7), and angiocentric gliomas (n = 2). MYB copy number abnormalities were disclosed using Affymetrix 6.0 SNP arrays and confirmed using interphase fluorescence in situ hybridization. Novel MYB amplifications that upregulate MYB RNA and protein expression were demonstrated in 2/14 diffuse astrocytomas. In addition, focal deletion of the terminal region of MYB was seen in 1 of 2 angiocentric gliomas (AGs). Increased expression of MYB was demonstrated by quantitative RT-PCR and immunohistochemistry. MYB upregulation at the protein level was demonstrated in a proportion of diffuse LGGs (60%), pilocytic astrocytomas (41%), and HGGs (19%), but abnormalities at the genomic level were only a feature of diffuse gliomas. Our data suggest that MYB may have a role in a subset of pediatric gliomas, through a variety of mechanisms in addition to MYB amplification and deletion.

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Title: MYB upregulation and genetic aberrations in a subset of pediatric low-grade gliomas
Authors: Ruth G. Tatevossian
Bo Tang
James Dalton
Tim Forshew
Andrew R. Lawson
Jing Ma
Geoff Neale
Sheila A. Shurtleff
Simon Bailey
Amar Gajjar
Suzanne J. Baker
Denise Sheer
David W. Ellison
Publication date: 01-12-2010
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 6/2010
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-010-0763-1

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MYB upregulation and genetic aberrations in a subset of pediatric low-grade gliomas

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