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Temporal lobe pleomorphic xanthoastrocytoma and acquired BRAF mutation in an adolescent with the constitutional 22q11.2 deletion syndrome

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Abstract

DiGeorge syndrome, or velocardiofacial syndrome (DGS/VCFS), is a rare and usually sporadic congenital genetic disorder resulting from a constitutional microdeletion at chromosome 22q11.2. While rare cases of malignancy have been described, likely due to underlying immunodeficiency, central nervous system tumors have not yet been reported. We describe an adolescent boy with DGS/VCFS who developed a temporal lobe pleomorphic xanthoastrocytoma. High-resolution single nucleotide polymorphism array studies of the tumor confirmed a constitutional 22q11.21 deletion, and revealed acquired gains, losses and copy number neutral loss of heterozygosity of several chromosomal regions, including a homozygous deletion of the CDKN2A/B locus. The tumor also demonstrated a common V600E mutation in the BRAF oncogene. This is the first reported case of a patient with DiGeorge syndrome developing a CNS tumor of any histology and expands our knowledge about low-grade CNS tumor molecular genetics.

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Abbreviations

BRAF:

B-Raf proto-oncogene serine/threonine-protein kinase

CNS:

Central nervous system

MRI:

Magnetic resonance image

PXA:

Pleomorphic xanthoastrocytoma

SNP:

Single nucleotide polymorphism

WHO:

World Health Organization

DGS/VCFS:

DiGeorge syndrome/velocardiofacial syndrome

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Acknowledgments

Supported in part by grants from the National Institutes of Health, CA 133173 and CA 46274 (JAB) and the N.B. Carter Neuro-Oncology Endowment Fund at Cook Children’s Medical Center, Fort Worth, TX (JCM).

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Authors and Affiliations

  1. Neurosciences Program, Hematology and Oncology Center, Cook Children’s Medical Center, 901 Seventh Avenue, Suite 220, Fort Worth, TX, 76104, USA

    Jeffrey C. Murray, David J. Donahue, Saleem I. Malik & Emily Z. Braly

  2. Department of Pathology, Cook Children’s Medical Center, 801 Seventh Avenue, Fort Worth, TX, 76104, USA

    Yvette B. Dzurik

  3. Department of Pediatrics, The Children’s Hospital of Philadelphia, Abramson Research Building, Room 1002, 3615 Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Margaret J. Dougherty & Katherine W. Eaton

  4. Departments of Pediatrics and Pathology, The Children’s Hospital of Philadelphia, Abramson Research Building, Room 1002, 3615 Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Jaclyn A. Biegel

Authors
  1. Jeffrey C. Murray
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  2. David J. Donahue
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  3. Saleem I. Malik
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  4. Yvette B. Dzurik
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  5. Emily Z. Braly
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  6. Margaret J. Dougherty
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  7. Katherine W. Eaton
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  8. Jaclyn A. Biegel
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Correspondence to Jeffrey C. Murray.

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Murray, J.C., Donahue, D.J., Malik, S.I. et al. Temporal lobe pleomorphic xanthoastrocytoma and acquired BRAF mutation in an adolescent with the constitutional 22q11.2 deletion syndrome. J Neurooncol 102, 509–514 (2011). https://doi.org/10.1007/s11060-010-0350-2

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  • DOI: https://doi.org/10.1007/s11060-010-0350-2

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