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

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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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Acknowledgments

This work was supported by the Pediatric Low-Grade Astrocytoma (PLGA) Foundation, the American Lebanese Syrian Associated Charities (ALSAC), the Samantha Dickson Brain Tumour Trust, and Cancer Research, UK.

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Authors and Affiliations

  1. Department of Pathology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA

    Ruth G. Tatevossian, Bo Tang, James Dalton, Sheila A. Shurtleff & David W. Ellison

  2. Centre for Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK

    Tim Forshew, Andrew R. Lawson & Denise Sheer

  3. Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children’s Research Hospital, Memphis, TN, 38105, USA

    Jing Ma & Geoff Neale

  4. Sir James Spence Institute of Child Health, Royal Victoria Infirmary, Newcastle upon Tyne, UK

    Simon Bailey

  5. Department of Oncology, St Jude Children’s Research Hospital, Memphis, TN, 38105, USA

    Amar Gajjar

  6. Department of Developmental Neurobiology, St Jude Children’s Research Hospital, Memphis, TN, 38105, USA

    Suzanne J. Baker

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  1. Ruth G. Tatevossian
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  2. Bo Tang
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  3. James Dalton
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  4. Tim Forshew
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Correspondence to Denise Sheer or David W. Ellison.

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Tatevossian, R.G., Tang, B., Dalton, J. et al. MYB upregulation and genetic aberrations in a subset of pediatric low-grade gliomas. Acta Neuropathol 120, 731–743 (2010). https://doi.org/10.1007/s00401-010-0763-1

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  • DOI: https://doi.org/10.1007/s00401-010-0763-1

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